{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T23:03:20Z","timestamp":1785366200190,"version":"3.55.0"},"reference-count":315,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Cancer immunotherapy has significantly advanced oncological care, offering durable responses for a subset of patients. However, the efficacy of these treatments is frequently hindered by primary and acquired resistance orchestrated by the tumor microenvironment (TME). Within the highly heterogeneous TME, multidirectional interactions between tumor cells, stromal components, and infiltrating immune cells actively suppress anti-tumor immunity. This review comprehensively examines the multifaceted immune regulatory mechanisms within the TME, with a specific focus on the immunosuppressive roles of tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs). We further explore how metabolic reprogramming\u2014such as the Warburg effect, lactate accumulation, and hypoxia\u2014creates a hostile niche that impairs effector T cell function and promotes immune evasion. Bridging basic research to clinical translation, we systematically evaluate current TME-targeted therapeutic strategies, including immune checkpoint inhibitors (ICIs), adoptive cell therapies, oncolytic viruses, and anti-angiogenic agents. The review also highlights emerging combinatorial approaches designed to remodel the immunosuppressive stroma and normalize the tumor vasculature. Finally, we discuss critical challenges in clinical application, such as tumor heterogeneity and the need for predictive biomarkers, emphasizing that personalized strategies tailored to specific TME phenotypes are essential for overcoming therapeutic resistance and improving patient outcomes.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1810065","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:10:51Z","timestamp":1780035051000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Immune regulatory mechanisms in the tumor microenvironment and their applications in cancer therapy: from basic research to clinical translation"],"prefix":"10.3389","volume":"17","author":[{"given":"Yafei","family":"Feng","sequence":"first","affiliation":[{"name":"The Second Hospital, Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"Department of Pharmacy, The Second Hospital, Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Hospital, Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"Department of Cardiology, The Second Hospital, Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyi","family":"Li","sequence":"additional","affiliation":[{"name":"The Second Hospital, Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"Department of Respiratory Medicine, The Second Hospital, Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuze","family":"Wang","sequence":"additional","affiliation":[{"name":"The Second Hospital, Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"Department of General Surgery, The Second Hospital, Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Second Hospital, Dalian Medical University","place":["Dalian, Liaoning, China"]},{"name":"Department of Pharmacy, The Second Hospital, Dalian Medical University","place":["Dalian, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1158\/2159-8290.cd-21-1059","article-title":"Hallmarks of cancer: New dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10673","article-title":"Cancer immunotherapy comes of age","volume":"480","author":"Mellman","year":"2011","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","article-title":"Oncology meets immunology: The cancer-immunity cycle","volume":"39","author":"Chen","year":"2013","journal-title":"Immunity"},{"key":"B4","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s13045-024-01578-x","article-title":"Recent developments in immunotherapy for gastrointestinal tract cancers","volume":"17","author":"Chong","year":"2024","journal-title":"J Hematol Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acr.2024.05.004","article-title":"Recent advances and progress in immunotherapy of solid cancers","volume":"164","author":"Kumar","year":"2024","journal-title":"Adv Cancer Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth","volume":"41","author":"de Visser","year":"2023","journal-title":"Cancer Cell"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.05.007","article-title":"Interrogation of the microenvironmental landscape in brain tumors reveals disease-specific alterations of immune cells","volume":"181","author":"Klemm","year":"2020","journal-title":"Cell"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032414-112049","article-title":"Coinhibitory pathways in immunotherapy for cancer","volume":"34","author":"Baumeister","year":"2016","journal-title":"Annu Rev Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-025-00986-3","article-title":"The tumor microenvironment's role in the response to immune checkpoint blockade","volume":"6","author":"Aliazis","year":"2025","journal-title":"Nat Cancer"},{"key":"B10","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12943-021-01316-8","article-title":"The cancer metabolic reprogramming and immune response","volume":"20","author":"Xia","year":"2021","journal-title":"Mol Cancer"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-021-00378-6","article-title":"Cancer metabolism: Looking forward","volume":"21","author":"Martinez-Reyes","year":"2021","journal-title":"Nat Rev Cancer"},{"key":"B12","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/s41392-020-00449-4","article-title":"Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy","volume":"6","author":"Tang","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-024-00714-6","article-title":"Towards targeting the breast cancer immune microenvironment","volume":"24","author":"Harris","year":"2024","journal-title":"Nat Rev Cancer"},{"key":"B14","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.semcancer.2013.12.008","article-title":"TGF-beta in CAF-mediated tumor growth and metastasis","volume":"25","author":"Calon","year":"2014","journal-title":"Semin Cancer Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-025-00832-9","article-title":"Regulatory T cells in the tumour microenvironment","volume":"25","author":"Imianowski","year":"2025","journal-title":"Nat Rev Cancer"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2015.1075112","article-title":"PD-L1 mediated the differentiation of tumor-infiltrating CD19(+) B lymphocytes and T cells in invasive breast cancer","volume":"5","author":"Guan","year":"2016","journal-title":"Oncoimmunology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nri3405","article-title":"Molecular mechanisms of T cell co-stimulation and co-inhibition","volume":"13","author":"Chen","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.coi.2015.12.007","article-title":"The urgent need to recover MHC class I in cancers for effective immunotherapy","volume":"39","author":"Garrido","year":"2016","journal-title":"Curr Opin Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.016","article-title":"Metabolic competition in the tumor microenvironment is a driver of cancer progression","volume":"162","author":"Chang","year":"2015","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.08.011","article-title":"LDHA-associated lactic acid production blunts tumor immunosurveillance by T and NK cells","volume":"24","author":"Brand","year":"2016","journal-title":"Cell Metab"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.2327","article-title":"Crosstalk between cancer and immune cells: Role of tumor-associated macrophages in the tumor microenvironment","volume":"8","author":"Wang","year":"2019","journal-title":"Cancer Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-022-00277-y","article-title":"Heterogeneity of the tumor immune microenvironment and its clinical relevance","volume":"11","author":"Jia","year":"2022","journal-title":"Exp Hematol Oncol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1103149","article-title":"Tumor-associated macrophage polarization in the inflammatory tumor microenvironment","volume":"13","author":"Zou","year":"2023","journal-title":"Front Oncol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.888713","article-title":"Shaping polarization of tumor-associated macrophages in cancer immunotherapy","volume":"13","author":"Gao","year":"2022","journal-title":"Front Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/s41698-024-00522-z","article-title":"Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance","volume":"8","author":"Wang","year":"2024","journal-title":"NPJ Precis Oncol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.5vmr0415-166r","article-title":"Macrophage responses to implants: Prospects for personalized medicine","volume":"98","author":"Kzhyshkowska","year":"2015","journal-title":"J Leukoc Biol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1038\/nrd.2018.169","article-title":"Targeting macrophages: Therapeutic approaches in cancer","volume":"17","author":"Cassetta","year":"2018","journal-title":"Nat Rev Drug Discov"},{"key":"B28","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1186\/s40425-017-0257-y","article-title":"Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy","volume":"5","author":"Cannarile","year":"2017","journal-title":"J Immunother Cancer"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010046","article-title":"Current strategies to target tumor-associated-macrophages to improve anti-tumor immune responses","volume":"9","author":"Anfray","year":"2019","journal-title":"Cells"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13886","article-title":"Interactions of NK cells and macrophages: From infections to cancer therapeutics","volume":"174","author":"Hooda","year":"2025","journal-title":"Immunology"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-08-238469","article-title":"Regulation of human NK-cell cytokine and chemokine production by target cell recognition","volume":"115","author":"Fauriat","year":"2010","journal-title":"Blood"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-017-2052-5","article-title":"Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression","volume":"66","author":"Fu","year":"2017","journal-title":"Cancer Immunol Immunother"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-16-2310","article-title":"Cellular and molecular identity of tumor-associated macrophages in glioblastoma","volume":"77","author":"Chen","year":"2017","journal-title":"Cancer Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4185","article-title":"The role of microglia and macrophages in glioma maintenance and progression","volume":"19","author":"Hambardzumyan","year":"2016","journal-title":"Nat Neurosci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.02.009","article-title":"The microenvironmental landscape of brain tumors","volume":"31","author":"Quail","year":"2017","journal-title":"Cancer Cell"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15080","article-title":"Tumour-associated macrophages secrete pleiotrophin to promote PTPRZ1 signalling in glioblastoma stem cells for tumour growth","volume":"8","author":"Shi","year":"2017","journal-title":"Nat Commun"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1026954","article-title":"Major pathways involved in macrophage polarization in cancer","volume":"13","author":"Kerneur","year":"2022","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27782","article-title":"CD8(+) cytotoxic T lymphocytes in cancer immunotherapy: A review","volume":"234","author":"Farhood","year":"2019","journal-title":"J Cell Physiol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-010-0824-2","article-title":"MHC-based detection of antigen-specific CD8 T cell responses","volume":"59","author":"Hadrup","year":"2010","journal-title":"Cancer Immunol Immun"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat Rev Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2015.03.001","article-title":"Immune checkpoint blockade: A common denominator approach to cancer therapy","volume":"27","author":"Topalian","year":"2015","journal-title":"Cancer Cell"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-019-0512-0","article-title":"Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: Breakthroughs or backups","volume":"20","author":"Andrews","year":"2019","journal-title":"Nat Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2020-000957","article-title":"TIGIT in cancer immunotherapy","volume":"8","author":"Chauvin","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(22)00226-1","article-title":"Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): Primary and follow-up analyses of a randomised, double-blind, phase 2 study","volume":"23","author":"Cho","year":"2022","journal-title":"Lancet Oncol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12528","article-title":"The ectonucleotidases CD39 and CD73: Novel checkpoint inhibitor targets","volume":"276","author":"Allard","year":"2017","journal-title":"Immunol Rev"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-020-0347-5","article-title":"T cell-engaging therapies - BiTEs and beyond","volume":"17","author":"Goebeler","year":"2020","journal-title":"Nat Rev Clin Oncol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.06.007","article-title":"De novo epigenetic programs inhibit PD-1 blockade-mediated T cell rejuvenation","volume":"170","author":"Ghoneim","year":"2017","journal-title":"Cell"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar6711","article-title":"CAR T cell immunotherapy for human cancer","volume":"359","author":"June","year":"2018","journal-title":"Science"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101212","article-title":"Differentiation of effector CD4 T cell populations","volume":"28","author":"Zhu","year":"2010","journal-title":"Annu Rev Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23291","article-title":"Activated monocytes in peritumoral stroma of hepatocellular carcinoma promote expansion of memory T helper 17 cells","volume":"51","author":"Kuang","year":"2010","journal-title":"Hepatology"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1192303","article-title":"The protective and pathogenic role of Th17 cell plasticity and function in the tumor microenvironment","volume":"14","author":"Pan","year":"2023","journal-title":"Front Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-019-0175-7","article-title":"Regulatory T cells in cancer immunosuppression - implications for anticancer therapy","volume":"16","author":"Togashi","year":"2019","journal-title":"Nat Rev Clin Oncol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12943-020-01234-1","article-title":"Regulatory T cells in tumor microenvironment: new mechanisms, potential therapeutic strategies and future prospects","volume":"19","author":"Li","year":"2020","journal-title":"Mol Cancer"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160062","article-title":"CTLA-4 control over Foxp3 regulatory T cell function","volume":"322","author":"Wing","year":"2008","journal-title":"Science"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1126\/science.1202947","article-title":"Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4","volume":"332","author":"Qureshi","year":"2011","journal-title":"Science"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1007\/bf00241263","article-title":"Cellular expression and tissue distribution of the human Lag-3-encoded protein, an MHC class-II ligand","volume":"39","author":"Huard","year":"1994","journal-title":"Immunogenetics"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0800185","article-title":"LAG-3 regulates plasmacytoid dendritic cell homeostasis","volume":"182","author":"Workman","year":"2009","journal-title":"J Immunol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2024.107241","article-title":"The immune checkpoint receptor LAG3: structure, function, and target for cancer immunotherapy","volume":"300","author":"Mariuzza","year":"2024","journal-title":"J Biol Chem"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2023.08.009","article-title":"Tertiary lymphoid structures and B cells: an intratumoral immunity cycle","volume":"56","author":"Fridman","year":"2023","journal-title":"Immunity"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-022-00466-1","article-title":"Tumour-infiltrating B cells: immunological mechanisms, clinical impact and therapeutic opportunities","volume":"22","author":"Laumont","year":"2022","journal-title":"Nat Rev Cancer"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.04.005","article-title":"Regulatory B cells: origin, phenotype, and function","volume":"42","author":"Rosser","year":"2015","journal-title":"Immunity"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200851","article-title":"B cells and cancer: to B or not to B","volume":"218","author":"Fridman","year":"2021","journal-title":"J Exp Med"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1922-8","article-title":"B cells and tertiary lymphoid structures promote immunotherapy response","volume":"577","author":"Helmink","year":"2020","journal-title":"Nature"},{"key":"B65","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1038\/s41577-019-0210-z","article-title":"Dendritic cells in cancer immunology and immunotherapy","volume":"20","author":"Wculek","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.09.006","article-title":"Dendritic cells and cancer immunity","volume":"37","author":"Gardner","year":"2016","journal-title":"Trends Immunol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1038\/nature06175","article-title":"Taking dendritic cells into medicine","volume":"449","author":"Steinman","year":"2007","journal-title":"Nature"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1328193","article-title":"Mechanisms underlying immunosuppression by regulatory cells","volume":"15","author":"Goldmann","year":"2024","journal-title":"Front Immunol"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2018.1431598","article-title":"Inhibition of IL-10 and TGF-beta receptors on dendritic cells enhances activation of effector T-cells to kill cholangiocarcinoma cells","volume":"14","author":"Thepmalee","year":"2018","journal-title":"Hum Vaccin Immunother"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.1056379","article-title":"Significance of exosomes in hepatocellular carcinoma","volume":"12","author":"Wang","year":"2022","journal-title":"Front Oncol"},{"key":"B71","article-title":"Role of NKG2D and its ligands in cancer immunotherapy","volume":"9","author":"Liu","year":"2019","journal-title":"Am J Cancer Res"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201948222","article-title":"Loss of NKG2D in murine NK cells leads to increased perforin production upon long-term stimulation with IL-2","volume":"50","author":"Prinz","year":"2020","journal-title":"Eur J Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5428.727","article-title":"Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA","volume":"285","author":"Bauer","year":"1999","journal-title":"Science"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-020711-075005","article-title":"Controlling natural killer cell responses: integration of signals for activation and inhibition","volume":"31","author":"Long","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022842","article-title":"Human tumour immune evasion via TGF-beta blocks NK cell activation but not survival allowing therapeutic restoration of anti-tumour activity","volume":"6","author":"Wilson","year":"2011","journal-title":"PloS One"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03038","article-title":"Influence of the tumor microenvironment on NK cell function in solid tumors","volume":"10","author":"Melaiu","year":"2019","journal-title":"Front Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903225","article-title":"DNAM-1\/CD155 interactions promote cytokine and NK cell-mediated suppression of poorly immunogenic melanoma metastases","volume":"184","author":"Chan","year":"2010","journal-title":"J Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-08-173914","article-title":"ATM-ATR-dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype","volume":"113","author":"Soriani","year":"2009","journal-title":"Blood"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.9980","article-title":"Fas ligand and lytic granule differentially control cytotoxic dynamics of natural killer cell against cancer target","volume":"7","author":"Zhu","year":"2016","journal-title":"Oncotarget"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.896228","article-title":"All about (NK cell-mediated) death in two acts and an unexpected encore: initiation, execution and activation of adaptive immunity","volume":"13","author":"Ramirez-Labrada","year":"2022","journal-title":"Front Immunol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1574742","article-title":"CAR-NK cell therapy: promise and challenges in solid tumors","volume":"16","author":"Balkhi","year":"2025","journal-title":"Front Immunol"},{"key":"B82","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/s41420-024-02077-1","article-title":"Emerging roles of CAR-NK cell therapies in tumor immunotherapy: current status and future directions","volume":"10","author":"Zhong","year":"2024","journal-title":"Cell Death Discov"},{"key":"B83","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13045-020-01014-w","article-title":"NK cell-based cancer immunotherapy: from basic biology to clinical development","volume":"14","author":"Liu","year":"2021","journal-title":"J Hematol Oncol"},{"key":"B84","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1093\/neuonc\/nop009","article-title":"TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients","volume":"12","author":"Crane","year":"2010","journal-title":"Neuro Oncol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awl205","article-title":"TGF-beta and metalloproteinases differentially suppress NKG2D ligand surface expression on Malignant glioma cells","volume":"129","author":"Eisele","year":"2006","journal-title":"Brain"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02683","article-title":"CAR-engineered NK cells for the treatment of glioblastoma: turning innate effectors into precision tools for cancer immunotherapy","volume":"10","author":"Burger","year":"2019","journal-title":"Front Immunol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(23)00112-2","article-title":"Repeated blood-brain barrier opening with an implantable ultrasound device for delivery of albumin-bound paclitaxel in patients with recurrent glioblastoma: a phase 1 trial","volume":"24","author":"Sonabend","year":"2023","journal-title":"Lancet Oncol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv375","article-title":"ErbB2\/HER2-specific NK cells for targeted therapy of glioblastoma","volume":"108","author":"Zhang","year":"2016","journal-title":"J Natl Cancer Inst"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noad087","article-title":"Intracranial injection of natural killer cells engineered with a HER2-targeted chimeric antigen receptor in patients with recurrent glioblastoma","volume":"25","author":"Burger","year":"2023","journal-title":"Neuro Oncol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1038\/nri2506","article-title":"Myeloid-derived suppressor cells as regulators of the immune system","volume":"9","author":"Gabrilovich","year":"2009","journal-title":"Nat Rev Immunol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12150","article-title":"Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards","volume":"7","author":"Bronte","year":"2016","journal-title":"Nat Commun"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1186\/2051-1426-1-10","article-title":"Myeloid derived suppressor cells - a new therapeutic target in the treatment of cancer","volume":"1","author":"Wesolowski","year":"2013","journal-title":"J Immunother Cancer"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines4040036","article-title":"The role of myeloid-derived suppressor cells (MDSC) in cancer progression","volume":"4","author":"Umansky","year":"2016","journal-title":"Vaccines (Basel)"},{"key":"B94","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1186\/s40425-019-0536-x","article-title":"The immune suppressive microenvironment of human gliomas depends on the accumulation of bone marrow-derived macrophages in the center of the lesion","volume":"7","author":"Pinton","year":"2019","journal-title":"J Immunother Cancer"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.2.989","article-title":"Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species","volume":"172","author":"Kusmartsev","year":"2004","journal-title":"J Immunol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-05-1299","article-title":"Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host","volume":"66","author":"Huang","year":"2006","journal-title":"Cancer Res"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-17-2460","article-title":"Metformin-induced reduction of CD39 and CD73 blocks myeloid-derived suppressor cell activity in patients with ovarian cancer","volume":"78","author":"Li","year":"2018","journal-title":"Cancer Res"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00771","article-title":"Myeloid derived suppressor cells interactions with natural killer cells and pro-angiogenic activities: roles in tumor progression","volume":"10","author":"Bruno","year":"2019","journal-title":"Front Immunol"},{"key":"B99","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.canlet.2006.12.012","article-title":"CCL2\/CCR2 pathway mediates recruitment of myeloid suppressor cells to cancers","volume":"252","author":"Huang","year":"2007","journal-title":"Cancer Lett"},{"key":"B100","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1038\/s41573-018-0004-1","article-title":"Turning foes to friends: targeting cancer-associated fibroblasts","volume":"18","author":"Chen","year":"2019","journal-title":"Nat Rev Drug Discov"},{"key":"B101","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s12943-021-01428-1","article-title":"Crosstalk between cancer-associated fibroblasts and immune cells in the tumor microenvironment: new findings and future perspectives","volume":"20","author":"Mao","year":"2021","journal-title":"Mol Cancer"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2019.00160","article-title":"ECM in the tumor microenvironment and its impact on cancer therapy","volume":"6","author":"Henke","year":"2019","journal-title":"Front Mol Biosci"},{"key":"B103","doi-asserted-by":"publisher","first-page":"5120","DOI":"10.1038\/s41467-020-18794-x","article-title":"Concepts of ECM remodelling in tumour progression and metastasis","volume":"11","author":"Winkler","year":"2020","journal-title":"Nat Commun"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-017-2003-1","article-title":"Tumor-associated fibrosis as a regulator of tumor immunity and response to immunotherapy","volume":"66","author":"Jiang","year":"2017","journal-title":"Cancer Immunol Immunother"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.7554\/elife.58688","article-title":"Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment","volume":"10","author":"Nicolas-Boluda","year":"2021","journal-title":"Elife"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0420-5","article-title":"Matrix stiffness induces a tumorigenic phenotype in mammary epithelium through changes in chromatin accessibility","volume":"3","author":"Stowers","year":"2019","journal-title":"Nat BioMed Eng"},{"key":"B107","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1186\/s13045-017-0408-0","article-title":"Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein","volume":"10","author":"Chen","year":"2017","journal-title":"J Hematol Oncol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.01.011","article-title":"Identification of a tumour immune barrier in the HCC microenvironment that determines the efficacy of immunotherapy","volume":"78","author":"Liu","year":"2023","journal-title":"J Hepatol"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1901931116","article-title":"Alphavbeta3-integrin regulates PD-L1 expression and is involved in cancer immune evasion","volume":"116","author":"Vannini","year":"2019","journal-title":"Proc Natl Acad Sci USA"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3726","article-title":"Hypoxia and the ECM: drivers of tumour metastasis","volume":"14","author":"Gilkes","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0038-z","article-title":"Every step of the way: integrins in cancer progression and metastasis","volume":"18","author":"Hamidi","year":"2018","journal-title":"Nat Rev Cancer"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201439246","article-title":"The ECM modulates the hallmarks of cancer","volume":"15","author":"Pickup","year":"2014","journal-title":"EMBO Rep"},{"key":"B113","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.semcancer.2014.07.009","article-title":"Focal adhesion signaling and therapy resistance in cancer","volume":"31","author":"Eke","year":"2015","journal-title":"Semin Cancer Biol"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605154","article-title":"Characterisation of fibronectin-mediated FAK signalling pathways in lung cancer cell migration and invasion","volume":"101","author":"Meng","year":"2009","journal-title":"Br J Cancer"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2023.01.007","article-title":"From gatekeepers to providers: regulation of immune functions by cancer-associated fibroblasts","volume":"9","author":"Arpinati","year":"2023","journal-title":"Trends Cancer"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1038\/nature25501","article-title":"TGFbeta attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells","volume":"554","author":"Mariathasan","year":"2018","journal-title":"Nature"},{"key":"B117","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nrc2965","article-title":"Integrins in cancer: biological implications and therapeutic opportunities","volume":"10","author":"Desgrosellier","year":"2010","journal-title":"Nat Rev Cancer"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201704053","article-title":"Cancer-associated fibroblasts promote directional cancer cell migration by aligning fibronectin","volume":"216","author":"Erdogan","year":"2017","journal-title":"J Cell Biol"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2016.73","article-title":"The biology and function of fibroblasts in cancer","volume":"16","author":"Kalluri","year":"2016","journal-title":"Nat Rev Cancer"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01835","article-title":"The dark side of fibroblasts: cancer-associated fibroblasts as mediators of immunosuppression in the tumor microenvironment","volume":"10","author":"Monteran","year":"2019","journal-title":"Front Immunol"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20162024","article-title":"Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer","volume":"214","author":"Ohlund","year":"2017","journal-title":"J Exp Med"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.cd-19-0094","article-title":"Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts","volume":"9","author":"Elyada","year":"2019","journal-title":"Cancer Discov"},{"key":"B123","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1158\/2159-8290.cd-18-0710","article-title":"IL1-induced JAK\/STAT signaling is antagonized by TGFbeta to shape CAF heterogeneity in pancreatic ductal adenocarcinoma","volume":"9","author":"Biffi","year":"2019","journal-title":"Cancer Discov"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.021","article-title":"VEGF in signaling and disease: beyond discovery and development","volume":"176","author":"Apte","year":"2019","journal-title":"Cell"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020518-114700","article-title":"Normalizing function of tumor vessels: progress, opportunities, and challenges","volume":"81","author":"Martin","year":"2019","journal-title":"Annu Rev Physiol"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20140559","article-title":"VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors","volume":"212","author":"Voron","year":"2015","journal-title":"J Exp Med"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20131916","article-title":"PD-L1 is a novel direct target of HIF-1alpha, and its blockade under hypoxia enhanced MDSC-mediated T cell activation","volume":"211","author":"Noman","year":"2014","journal-title":"J Exp Med"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-12-2796","article-title":"Acidity generated by the tumor microenvironment drives local invasion","volume":"73","author":"Estrella","year":"2013","journal-title":"Cancer Res"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3298","article-title":"Evolutionary dynamics of carcinogenesis and why targeted therapy does not work","volume":"12","author":"Gillies","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2015.02.004","article-title":"Contribution of acidic extracellular microenvironment of cancer-colonized bone to bone pain","volume":"1848","author":"Yoneda","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.01.007","article-title":"The hallmarks of cancer metabolism: still emerging","volume":"34","author":"Pavlova","year":"2022","journal-title":"Cell Metab"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg effect: how does it benefit cancer cells","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem Sci"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Science"},{"key":"B134","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1038\/cdd.2014.173","article-title":"Hexokinase II integrates energy metabolism and cellular protection: akting on mitochondria and TORCing to autophagy","volume":"22","author":"Roberts","year":"2015","journal-title":"Cell Death Differ"},{"key":"B135","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41568-019-0216-7","article-title":"The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism","volume":"20","author":"Hoxhaj","year":"2020","journal-title":"Nat Rev Cancer"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03442-1","article-title":"Cell-programmed nutrient partitioning in the tumour microenvironment","volume":"593","author":"Reinfeld","year":"2021","journal-title":"Nature"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-092910-154237","article-title":"Aerobic glycolysis: meeting the metabolic requirements of cell proliferation","volume":"27","author":"Lunt","year":"2011","journal-title":"Annu Rev Cell Dev Biol"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1007\/s10555-007-9055-1","article-title":"Hypoxia in cancer: significance and impact on clinical outcome","volume":"26","author":"Vaupel","year":"2007","journal-title":"Cancer Metastasis Rev"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2014.10.006","article-title":"Antiangiogenesis strategies revisited: from starving tumors to alleviating hypoxia","volume":"26","author":"Jain","year":"2014","journal-title":"Cancer Cell"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.51.32529","article-title":"Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1","volume":"271","author":"Semenza","year":"1996","journal-title":"J Biol Chem"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.02.002","article-title":"HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia","volume":"3","author":"Kim","year":"2006","journal-title":"Cell Metab"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.06.010","article-title":"Emerging roles of PKM2 in cell metabolism and cancer progression","volume":"23","author":"Luo","year":"2012","journal-title":"Trends Endocrinol Metab"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-677","article-title":"Regulation of angiogenesis by hypoxia: role of the HIF system","volume":"9","author":"Pugh","year":"2003","journal-title":"Nat Med"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1202702","article-title":"Tumor-derived lactate modifies antitumor immune response: effect on myeloid-derived suppressor cells and NK cells","volume":"191","author":"Husain","year":"2013","journal-title":"J Immunol"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-11-1272","article-title":"Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytes","volume":"72","author":"Calcinotto","year":"2012","journal-title":"Cancer Res"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1172\/jci36843","article-title":"Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice","volume":"118","author":"Sonveaux","year":"2008","journal-title":"J Clin Invest"},{"key":"B147","doi-asserted-by":"publisher","first-page":"3984","DOI":"10.4161\/cc.8.23.10238","article-title":"The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma","volume":"8","author":"Pavlides","year":"2009","journal-title":"Cell Cycle"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103627","article-title":"Lactate in the tumour microenvironment: from immune modulation to therapy","volume":"73","author":"Wang","year":"2021","journal-title":"EBioMedicine"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-03045-2","article-title":"Metabolic support of tumour-infiltrating regulatory T cells by lactic acid","volume":"591","author":"Watson","year":"2021","journal-title":"Nature"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-07-035972","article-title":"Inhibitory effect of tumor cell-derived lactic acid on human T cells","volume":"109","author":"Fischer","year":"2007","journal-title":"Blood"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.cir-18-0481","article-title":"Lactate-mediated acidification of tumor microenvironment induces apoptosis of liver-resident NK cells in colorectal liver metastasis","volume":"7","author":"Harmon","year":"2019","journal-title":"Cancer Immunol Res"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.4161\/onci.26383","article-title":"Tumor-derived lactate and myeloid-derived suppressor cells: Linking metabolism to cancer immunology","volume":"2","author":"Husain","year":"2013","journal-title":"Oncoimmunology"},{"key":"B153","doi-asserted-by":"publisher","DOI":"10.1038\/nature13490","article-title":"Functional polarization of tumour-associated macrophages by tumour-derived lactic acid","volume":"513","author":"Colegio","year":"2014","journal-title":"Nature"},{"key":"B154","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1614035114","article-title":"Gpr132 sensing of lactate mediates tumor-macrophage interplay to promote breast cancer metastasis","volume":"114","author":"Chen","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"B155","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.08.012","article-title":"Phosphoenolpyruvate is a metabolic checkpoint of anti-tumor T cell responses","volume":"162","author":"Ho","year":"2015","journal-title":"Cell"},{"key":"B156","doi-asserted-by":"publisher","DOI":"10.1126\/science.1211485","article-title":"Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses","volume":"334","author":"Anastasiou","year":"2011","journal-title":"Science"},{"key":"B157","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.06.043","article-title":"A mitochondrial switch promotes tumor metastasis","volume":"8","author":"Porporato","year":"2014","journal-title":"Cell Rep"},{"key":"B158","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3483","article-title":"Cancer metabolism: fatty acid oxidation in the limelight","volume":"13","author":"Carracedo","year":"2013","journal-title":"Nat Rev Cancer"},{"key":"B159","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/nrc.2016.71","article-title":"From Krebs to clinic: glutamine metabolism to cancer therapy","volume":"16","author":"Altman","year":"2016","journal-title":"Nat Rev Cancer"},{"key":"B160","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1146\/annurev.immunol.26.021607.090331","article-title":"PD-1 and its ligands in tolerance and immunity","volume":"26","author":"Keir","year":"2008","journal-title":"Annu Rev Immunol"},{"key":"B161","doi-asserted-by":"publisher","DOI":"10.1083\/jcb1976oia8","article-title":"Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2","volume":"209","author":"Yokosuka","year":"2012","journal-title":"J Exp Med"},{"key":"B162","doi-asserted-by":"publisher","DOI":"10.1126\/science.aar4060","article-title":"Cancer immunotherapy using checkpoint blockade","volume":"359","author":"Ribas","year":"2018","journal-title":"Science"},{"key":"B163","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1003466","article-title":"Improved survival with ipilimumab in patients with metastatic melanoma","volume":"363","author":"Hodi","year":"2010","journal-title":"N Engl J Med"},{"key":"B164","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1200690","article-title":"Safety, activity, and immune correlates of anti-PD-1 antibody in cancer","volume":"366","author":"Topalian","year":"2012","journal-title":"N Engl J Med"},{"key":"B165","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf0683","article-title":"Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent","volume":"355","author":"Kamphorst","year":"2017","journal-title":"Science"},{"key":"B166","doi-asserted-by":"publisher","DOI":"10.1038\/nri3108","article-title":"The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses","volume":"11","author":"Walker","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"B167","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0915174107","article-title":"PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors","volume":"107","author":"Curran","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"B168","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1302369","article-title":"Nivolumab plus ipilimumab in advanced melanoma","volume":"369","author":"Wolchok","year":"2013","journal-title":"N Engl J Med"},{"key":"B169","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1016\/j.immuni.2016.05.001","article-title":"Lag-3, Tim-3, and TIGIT: Co-inhibitory receptors with specialized functions in immune regulation","volume":"44","author":"Anderson","year":"2016","journal-title":"Immunity"},{"key":"B170","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s13045-023-01499-1","article-title":"Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy","volume":"16","author":"Cai","year":"2023","journal-title":"J Hematol Oncol"},{"key":"B171","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1701019","article-title":"Myeloid-derived suppressor cells: Immune-suppressive cells that impair antitumor immunity and are sculpted by their environment","volume":"200","author":"Ostrand-Rosenberg","year":"2018","journal-title":"J Immunol"},{"key":"B172","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1126\/science.aaa8172","article-title":"The future of immune checkpoint therapy","volume":"348","author":"Sharma","year":"2015","journal-title":"Science"},{"key":"B173","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/bjc.2017.434","article-title":"Mechanisms of resistance to immune checkpoint inhibitors","volume":"118","author":"Jenkins","year":"2018","journal-title":"Br J Cancer"},{"key":"B174","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1604958","article-title":"Mutations associated with acquired resistance to PD-1 blockade in melanoma","volume":"375","author":"Zaretsky","year":"2016","journal-title":"N Engl J Med"},{"key":"B175","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1716948","article-title":"Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC","volume":"378","author":"Socinski","year":"2018","journal-title":"N Engl J Med"},{"key":"B176","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1097\/COC.0000000000000239","article-title":"CTLA-4 and PD-1 pathways: Similarities, differences, and implications of their inhibition","volume":"39","author":"Buchbinder","year":"2016","journal-title":"Am J Clin Oncol"},{"key":"B177","doi-asserted-by":"publisher","DOI":"10.7150\/thno.58390","article-title":"Turning cold tumors into hot tumors by improving T-cell infiltration","volume":"11","author":"Liu","year":"2021","journal-title":"Theranostics"},{"key":"B178","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(19)30388-2","article-title":"Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study","volume":"20","author":"Robert","year":"2019","journal-title":"Lancet Oncol"},{"key":"B179","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.10.004","article-title":"Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer","volume":"373","author":"Borghaei","year":"2015","journal-title":"N Engl J Med"},{"key":"B180","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1712126","article-title":"Nivolumab plus ipilimumab versus sunitinib in advanced renal-cell carcinoma","volume":"378","author":"Motzer","year":"2018","journal-title":"N Engl J Med"},{"key":"B181","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01569-z","article-title":"LAG-3 as the third checkpoint inhibitor","volume":"24","author":"Aggarwal","year":"2023","journal-title":"Nat Immunol"},{"key":"B182","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0014-x","article-title":"Understanding the tumor immune microenvironment (TIME) for effective therapy","volume":"24","author":"Binnewies","year":"2018","journal-title":"Nat Med"},{"key":"B183","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, adaptive, and acquired resistance to cancer immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell"},{"key":"B184","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1146\/annurev-cancerbio-070220-111016","article-title":"Central role of the antigen-presentation and interferon-\u03b3 pathways in resistance to immune checkpoint blockade","volume":"6","author":"Paschen","year":"2022","journal-title":"Annu Rev Cancer Biol"},{"key":"B185","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra1703481","article-title":"Immune-related adverse events associated with immune checkpoint blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N Engl J Med"},{"key":"B186","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.3923","article-title":"Fatal toxic effects associated with immune checkpoint inhibitors: A systematic review and meta-analysis","volume":"4","author":"Wang","year":"2018","journal-title":"JAMA Oncol"},{"key":"B187","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/nejmoa2407417","article-title":"Final, 10-year outcomes with nivolumab plus ipilimumab in advanced melanoma","volume":"392","author":"Wolchok","year":"2025","journal-title":"N Engl J Med"},{"key":"B188","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdy551","article-title":"Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors","volume":"30","author":"Heinhuis","year":"2019","journal-title":"Ann Oncol"},{"key":"B189","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2018.29","article-title":"Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges","volume":"15","author":"Fukumura","year":"2018","journal-title":"Nat Rev Clin Oncol"},{"key":"B190","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1801005","article-title":"Pembrolizumab plus chemotherapy in metastatic non-small-cell lung cancer","volume":"378","author":"Gandhi","year":"2018","journal-title":"N Engl J Med"},{"key":"B191","doi-asserted-by":"publisher","DOI":"10.1111\/cas.15816","article-title":"Pembrolizumab plus chemotherapy in Japanese patients with metastatic squamous non-small-cell lung cancer in KEYNOTE-407","volume":"114","author":"Sugawara","year":"2023","journal-title":"Cancer Sci"},{"key":"B192","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(23)00727-4","article-title":"Pembrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer (KEYNOTE-966): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"401","author":"Kelley","year":"2023","journal-title":"Lancet"},{"key":"B193","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s12943-023-01800-3","article-title":"Co-inhibition of TIGIT and PD-1\/PD-L1 in cancer immunotherapy: Mechanisms and clinical trials","volume":"22","author":"Chu","year":"2023","journal-title":"Mol Cancer"},{"key":"B194","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1212209","article-title":"Inhibitors of the CD73-adenosinergic checkpoint as promising combinatory agents for conventional and advanced cancer immunotherapy","volume":"14","author":"Kurago","year":"2023","journal-title":"Front Immunol"},{"key":"B195","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2019-000433","article-title":"Dual targeting of TGF-beta and PD-L1 via a bifunctional anti-PD-L1\/TGF-betaRII agent: status of preclinical and clinical advances","volume":"8","author":"Lind","year":"2020","journal-title":"J Immunother Cancer"},{"key":"B196","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaa4967","article-title":"Adoptive cell transfer as personalized immunotherapy for human cancer","volume":"348","author":"Rosenberg","year":"2015","journal-title":"Science"},{"key":"B197","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1709866","article-title":"Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia","volume":"378","author":"Maude","year":"2018","journal-title":"N Engl J Med"},{"key":"B198","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1910607","article-title":"Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors","volume":"382","author":"Liu","year":"2020","journal-title":"N Engl J Med"},{"key":"B199","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-020-0462-y","article-title":"Human chimeric antigen receptor macrophages for cancer immunotherapy","volume":"38","author":"Klichinsky","year":"2020","journal-title":"Nat Biotechnol"},{"key":"B200","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-062315-120245","article-title":"CAR T cell therapy for solid tumors","volume":"68","author":"Newick","year":"2017","journal-title":"Annu Rev Med"},{"key":"B201","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.cir-13-0027","article-title":"Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity","volume":"2","author":"Wang","year":"2014","journal-title":"Cancer Immunol Res"},{"key":"B202","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1101\/2021.12.17.473184","article-title":"Targeting macrophages with CAR-T cells delays solid tumor progression and enhances anti-tumor immunity","volume":"30","author":"Sanchez-Paulete","year":"2022","journal-title":"Mol Ther"},{"key":"B203","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-20893-2","article-title":"CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy","volume":"12","author":"Rodriguez-Garcia","year":"2021","journal-title":"Nat Commun"},{"key":"B204","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2005.10.012","article-title":"TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance","volume":"8","author":"Thomas","year":"2005","journal-title":"Cancer Cell"},{"key":"B205","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.832645","article-title":"Armored BCMA CAR T cells eliminate multiple myeloma and are resistant to the suppressive effects of TGF-beta","volume":"13","author":"Alabanza","year":"2022","journal-title":"Front Immunol"},{"key":"B206","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.05.003","article-title":"Dominant-negative TGF-beta receptor enhances PSMA-targeted human CAR T cell proliferation and augments prostate cancer eradication","volume":"26","author":"Kloss","year":"2018","journal-title":"Mol Ther"},{"key":"B207","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-022-03290-6","article-title":"Dominant-negative transforming growth factor-beta receptor-armoured mesothelin-targeted chimeric antigen receptor T cells slow tumour growth in a mouse model of ovarian cancer","volume":"72","author":"Li","year":"2023","journal-title":"Cancer Immunol Immunother"},{"key":"B208","doi-asserted-by":"publisher","first-page":"482","DOI":"10.1186\/s12967-021-03146-0","article-title":"CRISPR\/Cas9-mediated TGFbetaRII disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells in vitro","volume":"19","author":"Alishah","year":"2021","journal-title":"J Transl Med"},{"key":"B209","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.212.supp.1394.5643","article-title":"Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism","volume":"25","author":"Peralta","year":"2024","journal-title":"Nat Immunol"},{"key":"B210","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02153-3","article-title":"Inhibition of ENT1 relieves intracellular adenosine-mediated T cell suppression in cancer","volume":"26","author":"Sanders","year":"2025","journal-title":"Nat Immunol"},{"key":"B211","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.04.051","article-title":"Engineered tumor-targeted T cells mediate enhanced anti-tumor efficacy both directly and through activation of the endogenous immune system","volume":"23","author":"Avanzi","year":"2018","journal-title":"Cell Rep"},{"key":"B212","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s00262-024-03909-w","article-title":"CCR5 and IL-12 co-expression in CAR T cells improves antitumor efficacy by reprogramming tumor microenvironment in solid tumors","volume":"74","author":"Tian","year":"2025","journal-title":"Cancer Immunol Immunother"},{"key":"B213","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4478","article-title":"A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects","volume":"24","author":"Kagoya","year":"2018","journal-title":"Nat Med"},{"key":"B214","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41416-018-0325-1","article-title":"Teaching an old dog new tricks: next-generation CAR T cells","volume":"120","author":"Tokarew","year":"2019","journal-title":"Br J Cancer"},{"key":"B215","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2022.2114254","article-title":"Current updates on generations, approvals, and clinical trials of CAR T-cell therapy","volume":"18","author":"Asmamaw Dejenie","year":"2022","journal-title":"Hum Vaccin Immunother"},{"key":"B216","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines13040857","article-title":"The role of NK cells in cancer immunotherapy: mechanisms, evasion strategies, and therapeutic advances","volume":"13","author":"Morcillo-Martin-Romo","year":"2025","journal-title":"Biomedicines"},{"key":"B217","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s40164-025-00633-8","article-title":"The clinical landscape of CAR NK cells","volume":"14","author":"Jorgensen","year":"2025","journal-title":"Exp Hematol Oncol"},{"key":"B218","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2024-010822","article-title":"Co-expression of IL-15 and CCL21 strengthens CAR-NK cells to eliminate tumors in concert with T cells and equips them with PI3K\/AKT\/mTOR signal signature","volume":"13","author":"Wang","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B219","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.726985","article-title":"A novel Sushi-IL15-PD1 CAR-NK92 cell line with enhanced and PD-L1 targeted cytotoxicity against pancreatic cancer cells","volume":"12","author":"Xu","year":"2022","journal-title":"Front Oncol"},{"key":"B220","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02785-8","article-title":"Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19(+) B cell tumors: a phase 1\/2 trial","volume":"30","author":"Marin","year":"2024","journal-title":"Nat Med"},{"key":"B221","doi-asserted-by":"publisher","DOI":"10.1101\/2023.07.21.544585","article-title":"Tumor-reactive T cell clonotype dynamics underlying clinical response to TIL therapy in melanoma","volume":"57","author":"Chiffelle","year":"2024","journal-title":"Immunity"},{"key":"B222","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005755","article-title":"Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144\u201301 study","volume":"10","author":"Chesney","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B223","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2446","article-title":"A human memory T cell subset with stem cell-like properties","volume":"17","author":"Gattinoni","year":"2011","journal-title":"Nat Med"},{"key":"B224","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/nm.4241","article-title":"T memory stem cells in health and disease","volume":"23","author":"Gattinoni","year":"2017","journal-title":"Nat Med"},{"key":"B225","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-431718","article-title":"IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors","volume":"121","author":"Cieri","year":"2013","journal-title":"Blood"},{"key":"B226","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1982","article-title":"Wnt signaling arrests effector T cell differentiation and generates CD8+ memory stem cells","volume":"15","author":"Gattinoni","year":"2009","journal-title":"Nat Med"},{"key":"B227","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0010-1","article-title":"Determinants of response and resistance to CD19 chimeric antigen receptor (CAR) T cell therapy of chronic lymphocytic leukemia","volume":"24","author":"Fraietta","year":"2018","journal-title":"Nat Med"},{"key":"B228","doi-asserted-by":"publisher","DOI":"10.1056\/nejmra072739","article-title":"Cancer immunology","volume":"358","author":"Finn","year":"2008","journal-title":"N Engl J Med"},{"key":"B229","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-1300-4_4","article-title":"Cancer immunotherapy via dendritic cells","volume":"12","author":"Palucka","year":"2012","journal-title":"Nat Rev Cancer"},{"key":"B230","doi-asserted-by":"publisher","DOI":"10.5114\/aoms.2012.31610","article-title":"Sipuleucel-T immunotherapy for castration-resistant prostate cancer. A systematic review and meta-analysis","volume":"8","author":"Kawalec","year":"2012","journal-title":"Arch Med Sci"},{"key":"B231","doi-asserted-by":"publisher","DOI":"10.1038\/nature22991","article-title":"An immunogenic personal neoantigen vaccine for patients with melanoma","volume":"547","author":"Ott","year":"2017","journal-title":"Nature"},{"key":"B232","doi-asserted-by":"publisher","DOI":"10.1038\/nature23003","article-title":"Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer","volume":"547","author":"Sahin","year":"2017","journal-title":"Nature"},{"key":"B233","doi-asserted-by":"publisher","DOI":"10.1007\/s10238-024-01436-7","article-title":"Personalized neoantigen cancer vaccines: current progression, challenges and a bright future","volume":"24","author":"Wu","year":"2024","journal-title":"Clin Exp Med"},{"key":"B234","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-025-01670-w","article-title":"Cancer vaccines: current status and future directions","volume":"18","author":"Zhou","year":"2025","journal-title":"J Hematol Oncol"},{"key":"B235","doi-asserted-by":"publisher","DOI":"10.3390\/biom14040503","article-title":"Recent findings on therapeutic cancer vaccines: an updated review","volume":"14","author":"Sheikhlary","year":"2024","journal-title":"Biomolecules"},{"key":"B236","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay9013","article-title":"cGAS-STING-mediated DNA sensing maintains CD8(+) T cell stemness and promotes antitumor T cell therapy","volume":"12","author":"Li","year":"2020","journal-title":"Sci Transl Med"},{"key":"B237","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1007\/s10238-025-01691-2","article-title":"Oncolytic virotherapy and tumor microenvironment modulation","volume":"25","author":"Rivera-Orellana","year":"2025","journal-title":"Clin Exp Med"},{"key":"B238","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2025.03.035","article-title":"Oncolytic viruses as cancer therapeutics: from mechanistic insights to clinical translation","volume":"33","author":"Alwithenani","year":"2025","journal-title":"Mol Ther"},{"key":"B239","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2017.1412896","article-title":"Talimogene laherparepvec: first in class oncolytic virotherapy","volume":"14","author":"Conry","year":"2018","journal-title":"Hum Vaccin Immunother"},{"key":"B240","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-009-0809-6","article-title":"Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma","volume":"17","author":"Kaufman","year":"2010","journal-title":"Ann Surg Oncol"},{"key":"B241","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.035","article-title":"Oncolytic virotherapy promotes intratumoral T cell infiltration and improves anti-PD-1 immunotherapy","volume":"170","author":"Ribas","year":"2017","journal-title":"Cell"},{"key":"B242","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-016-5286-0","article-title":"Patterns of clinical response with talimogene laherparepvec (T-VEC) in patients with melanoma treated in the OPTiM phase III clinical trial","volume":"23","author":"Andtbacka","year":"2016","journal-title":"Ann Surg Oncol"},{"key":"B243","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2024947","article-title":"Oncolytic HSV-1 G207 immunovirotherapy for pediatric high-grade gliomas","volume":"384","author":"Friedman","year":"2021","journal-title":"N Engl J Med"},{"key":"B244","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.12.055","article-title":"Persistent T cell activation and cytotoxicity against glioblastoma following single oncolytic virus treatment in a clinical trial","volume":"189","author":"Meylan","year":"2026","journal-title":"Cell"},{"key":"B245","doi-asserted-by":"publisher","DOI":"10.1200\/jco.22.00343","article-title":"Randomized, double-blind, placebo-controlled, global phase III trial of talimogene laherparepvec combined with pembrolizumab for advanced melanoma","volume":"41","author":"Chesney","year":"2023","journal-title":"J Clin Oncol"},{"key":"B246","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-006270","article-title":"Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial","volume":"11","author":"Chesney","year":"2023","journal-title":"J Immunother Cancer"},{"key":"B247","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s11912-022-01341-w","article-title":"Oncolytic viruses and cancer immunotherapy","volume":"25","author":"Malhotra","year":"2023","journal-title":"Curr Oncol Rep"},{"key":"B248","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/978-3-319-67577-0_13","article-title":"Immunotherapeutic targeting of tumor-associated blood vessels","volume":"1036","author":"Fabian","year":"2017","journal-title":"Adv Exp Med Biol"},{"key":"B249","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-13-3696","article-title":"Releasing pressure in tumors: what do we know so far and where do we go from here? A review","volume":"74","author":"Ariffin","year":"2014","journal-title":"Cancer Res"},{"key":"B250","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1387198","article-title":"Signaling crosstalk between tumor endothelial cells and immune cells in the microenvironment of solid tumors","volume":"12","author":"Xu","year":"2024","journal-title":"Front Cell Dev Biol"},{"key":"B251","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00978","article-title":"Targeting VEGF\/VEGFR to modulate antitumor immunity","volume":"9","author":"Yang","year":"2018","journal-title":"Front Immunol"},{"key":"B252","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aay0555","article-title":"VEGF-A drives TOX-dependent T cell exhaustion in anti-PD-1-resistant microsatellite stable colorectal cancers","volume":"4","author":"Kim","year":"2019","journal-title":"Sci Immunol"},{"key":"B253","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-020-00500-y","article-title":"Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity","volume":"52","author":"Lee","year":"2020","journal-title":"Exp Mol Med"},{"key":"B254","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03867-5","article-title":"Pembrolizumab plus axitinib versus sunitinib for advanced clear cell renal cell carcinoma: 5-year survival and biomarker analyses of the phase 3 KEYNOTE-426 trial","volume":"31","author":"Rini","year":"2025","journal-title":"Nat Med"},{"key":"B255","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1915745","article-title":"Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma","volume":"382","author":"Finn","year":"2020","journal-title":"N Engl J Med"},{"key":"B256","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12624","article-title":"Atezolizumab in combination with bevacizumab enhances antigen-specific T-cell migration in metastatic renal cell carcinoma","volume":"7","author":"Wallin","year":"2016","journal-title":"Nat Commun"},{"key":"B257","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01023","article-title":"Exploring the immunological mechanisms underlying the anti-vascular endothelial growth factor activity in tumors","volume":"10","author":"de Aguiar","year":"2019","journal-title":"Front Immunol"},{"key":"B258","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2108330","article-title":"Lenvatinib plus pembrolizumab for advanced endometrial cancer","volume":"386","author":"Makker","year":"2022","journal-title":"N Engl J Med"},{"key":"B259","doi-asserted-by":"publisher","DOI":"10.1200\/jco.19.02627","article-title":"Lenvatinib plus pembrolizumab in patients with advanced endometrial cancer","volume":"38","author":"Makker","year":"2020","journal-title":"J Clin Oncol"},{"key":"B260","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-10-0171","article-title":"Angiopoietin-2 TIEs up macrophages in tumor angiogenesis","volume":"17","author":"De Palma","year":"2011","journal-title":"Clin Cancer Res"},{"key":"B261","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1525360113","article-title":"Ang-2\/VEGF bispecific antibody reprograms macrophages and resident microglia to anti-tumor phenotype and prolongs glioblastoma survival","volume":"113","author":"Kloepper","year":"2016","journal-title":"Proc Natl Acad Sci USA"},{"key":"B262","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2015.07.006","article-title":"A phase II trial of trebananib (AMG 386; IND#111071), a selective angiopoietin 1\/2 neutralizing peptibody, in patients with persistent\/recurrent carcinoma of the endometrium: An NRG\/Gynecologic Oncology Group trial","volume":"138","author":"Moore","year":"2015","journal-title":"Gynecol Oncol"},{"key":"B263","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-17-1588","article-title":"First-in-human phase I study of single-agent vanucizumab, a first-in-class bispecific anti-angiopoietin-2\/anti-VEGF-A antibody, in adult patients with advanced solid tumors","volume":"24","author":"Hidalgo","year":"2018","journal-title":"Clin Cancer Res"},{"key":"B264","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(18)30937-9","article-title":"Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased alpha-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"20","author":"Zhu","year":"2019","journal-title":"Lancet Oncol"},{"key":"B265","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(19)30458-9","article-title":"Ramucirumab plus pembrolizumab in patients with previously treated advanced non-small-cell lung cancer, gastro-oesophageal cancer, or urothelial carcinomas (JVDF): a multicohort, non-randomised, open-label, phase 1a\/b trial","volume":"20","author":"Herbst","year":"2019","journal-title":"Lancet Oncol"},{"key":"B266","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12102985","article-title":"Ramucirumab in combination with pembrolizumab in treatment-naive advanced gastric or GEJ adenocarcinoma: Safety and antitumor activity from the phase 1a\/b JVDF trial","volume":"12","author":"Chau","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B267","doi-asserted-by":"publisher","DOI":"10.1200\/jco.22.00912","article-title":"Phase II randomized study of ramucirumab and pembrolizumab versus standard of care in advanced non-small-cell lung cancer previously treated with immunotherapy-Lung-MAP S1800A","volume":"40","author":"Reckamp","year":"2022","journal-title":"J Clin Oncol"},{"key":"B268","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2022.06.003","article-title":"A phase 2 study of docetaxel, ramucirumab, and pembrolizumab for patients with metastatic or recurrent non-small-cell lung cancer (NSCLC) who progressed on platinum-doublet and PD-1\/PD-L1 blockade","volume":"23","author":"Osta","year":"2022","journal-title":"Clin Lung Cancer"},{"key":"B269","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(19)30634-5","article-title":"Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial","volume":"20","author":"Nakagawa","year":"2019","journal-title":"Lancet Oncol"},{"key":"B270","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-020-0273-y","article-title":"Metabolism of immune cells in cancer","volume":"20","author":"Leone","year":"2020","journal-title":"Nat Rev Cancer"},{"key":"B271","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/s41423-021-00727-3","article-title":"The therapeutic implications of immunosuppressive tumor aerobic glycolysis","volume":"19","author":"Reinfeld","year":"2022","journal-title":"Cell Mol Immunol"},{"key":"B272","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-15-1743","article-title":"Neutralization of tumor acidity improves antitumor responses to immunotherapy","volume":"76","author":"Pilon-Thomas","year":"2016","journal-title":"Cancer Res"},{"key":"B273","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-07-5575","article-title":"Bicarbonate increases tumor pH and inhibits spontaneous metastases","volume":"69","author":"Robey","year":"2009","journal-title":"Cancer Res"},{"key":"B274","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11040450","article-title":"Blockade of lactate dehydrogenase-A (LDH-A) improves efficacy of anti-programmed cell death-1 (PD-1) therapy in melanoma","volume":"11","author":"Daneshmandi","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B275","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-22-2263","article-title":"A phase I dose-escalation study of AZD3965, an oral monocarboxylate transporter 1 inhibitor, in patients with advanced cancer","volume":"29","author":"Halford","year":"2023","journal-title":"Clin Cancer Res"},{"key":"B276","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.163030","article-title":"Inhibition of monocarboxyate transporter 1 by AZD3965 as a novel therapeutic approach for diffuse large B-cell lymphoma and Burkitt lymphoma","volume":"102","author":"Noble","year":"2017","journal-title":"Haematologica"},{"key":"B277","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605251103","article-title":"A2A adenosine receptor protects tumors from antitumor T cells","volume":"103","author":"Ohta","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"B278","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.trecan.2016.01.003","article-title":"Anti-CD73 in cancer immunotherapy: awakening new opportunities","volume":"2","author":"Antonioli","year":"2016","journal-title":"Trends Cancer"},{"key":"B279","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1158\/2159-8290.cd-19-0980","article-title":"Adenosine 2A receptor blockade as an immunotherapy for treatment-refractory renal cell cancer","volume":"10","author":"Fong","year":"2020","journal-title":"Cancer Discov"},{"key":"B280","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyad216.022","article-title":"Phase 1b\/2 trial of ipilimumab, nivolumab, and ciforadenant (INC) (adenosine A2a receptor antagonist) in first-line advanced renal cell carcinoma","volume":"28","author":"Beckermann","year":"2023","journal-title":"Oncologist"},{"key":"B281","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11-190934","article-title":"Adenosine promotes alternative macrophage activation via A2A and A2B receptors","volume":"26","author":"Csoka","year":"2012","journal-title":"FASEB J"},{"key":"B282","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2012.10.001","article-title":"Indoleamine 2,3 dioxygenase and metabolic control of immune responses","volume":"34","author":"Munn","year":"2013","journal-title":"Trends Immunol"},{"key":"B283","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(19)30274-8","article-title":"Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301\/KEYNOTE-252): a phase 3, randomised, double-blind study","volume":"20","author":"Long","year":"2019","journal-title":"Lancet Oncol"},{"key":"B284","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2017.143","article-title":"IDO1 in cancer: a Gemini of immune checkpoints","volume":"15","author":"Zhai","year":"2018","journal-title":"Cell Mol Immunol"},{"key":"B285","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.09.031","article-title":"L-arginine modulates T cell metabolism and enhances survival and anti-tumor activity","volume":"167","author":"Geiger","year":"2016","journal-title":"Cell"},{"key":"B286","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1417636112","article-title":"Immune-mediated antitumor effect by type 2 diabetes drug, metformin","volume":"112","author":"Eikawa","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"B287","doi-asserted-by":"publisher","DOI":"10.1038\/nature21349","article-title":"Elements of cancer immunity and the cancer-immune set point","volume":"541","author":"Chen","year":"2017","journal-title":"Nature"},{"key":"B288","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2015.03.004","article-title":"Immune evasion in cancer: mechanistic basis and therapeutic strategies","volume":"35","author":"Vinay","year":"2015","journal-title":"Semin Cancer Biol"},{"key":"B289","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.immuni.2019.06.025","article-title":"Inflammation and cancer: triggers, mechanisms, and consequences","volume":"51","author":"Greten","year":"2019","journal-title":"Immunity"},{"key":"B290","doi-asserted-by":"publisher","DOI":"10.1038\/nri2343","article-title":"How regulatory T cells work","volume":"8","author":"Vignali","year":"2008","journal-title":"Nat Rev Immunol"},{"key":"B291","doi-asserted-by":"publisher","DOI":"10.1038\/srep15179","article-title":"Prognostic value of tumor-infiltrating FoxP3 regulatory T cells in cancers: a systematic review and meta-analysis","volume":"5","author":"Shang","year":"2015","journal-title":"Sci Rep-Uk"},{"key":"B292","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1093\/intimm\/dxu079","article-title":"CCR4 and its ligands: from bench to bedside","volume":"27","author":"Yoshie","year":"2015","journal-title":"Int Immunol"},{"key":"B293","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.ccr-21-2781","article-title":"Mogamulizumab in combination with nivolumab in a phase I\/II study of patients with locally advanced or metastatic solid tumors","volume":"28","author":"Hong","year":"2022","journal-title":"Clin Cancer Res"},{"key":"B294","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2022008327","article-title":"Identifying highly active anti-CCR4 CAR T cells for the treatment of T-cell lymphoma","volume":"7","author":"Watanabe","year":"2023","journal-title":"Blood Adv"},{"key":"B295","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.01.004","article-title":"The nature of myeloid-derived suppressor cells in the tumor microenvironment","volume":"37","author":"Kumar","year":"2016","journal-title":"Trends Immunol"},{"key":"B296","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080132","article-title":"Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein","volume":"205","author":"Cheng","year":"2008","journal-title":"J Exp Med"},{"key":"B297","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.04.014","article-title":"Cxcr2 inhibition profoundly suppresses metastases and augments immunotherapy in pancreatic ductal adenocarcinoma","volume":"29","author":"Steele","year":"2016","journal-title":"Cancer Cell"},{"key":"B298","doi-asserted-by":"publisher","DOI":"10.1172\/jci60083","article-title":"Stat3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients","volume":"123","author":"Vasquez-Dunddel","year":"2013","journal-title":"J Clin Invest"},{"key":"B299","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(16)00078-4","article-title":"Targeting tumour-associated macrophages with ccr2 inhibition in combination with folfirinox in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial","volume":"17","author":"Nywening","year":"2016","journal-title":"Lancet Oncol"},{"key":"B300","doi-asserted-by":"publisher","DOI":"10.1038\/nature20554","article-title":"Overcoming resistance to checkpoint blockade therapy by targeting pi3k\u03b3 in myeloid cells","volume":"539","author":"De Henau","year":"2016","journal-title":"Nature"},{"key":"B301","doi-asserted-by":"publisher","DOI":"10.1038\/nature19834","article-title":"Pi3kgamma is a molecular switch that controls immune suppression","volume":"539","author":"Kaneda","year":"2016","journal-title":"Nature"},{"key":"B302","doi-asserted-by":"publisher","DOI":"10.1186\/s40425-019-0806-7","article-title":"Crispr-cas9 disruption of pd-1 enhances activity of universal egfrviii car t cells in a preclinical model of human glioblastoma","volume":"7","author":"Choi","year":"2019","journal-title":"J Immunother Cancer"},{"key":"B303","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(19)30764-0","article-title":"Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (enliven): a randomised phase 3 trial","volume":"394","author":"Tap","year":"2019","journal-title":"Lancet"},{"key":"B304","doi-asserted-by":"publisher","DOI":"10.1200\/jco.22.01794","article-title":"Magrolimab in combination with azacitidine in patients with higher-risk myelodysplastic syndromes: final results of a phase ib study","volume":"41","author":"Sallman","year":"2023","journal-title":"J Clin Oncol"},{"key":"B305","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2024027506","article-title":"The enhance-3 study: venetoclax and azacitidine plus magrolimab or placebo for untreated aml unfit for intensive therapy","volume":"146","author":"Daver","year":"2025","journal-title":"Blood"},{"key":"B306","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1182\/blood.2024027408","article-title":"Magrolimab plus azacitidine vs physician's choice for untreated tp53-mutated acute myeloid leukemia: the enhance-2 study","volume":"146","author":"Zeidner","year":"2025","journal-title":"Blood"},{"key":"B307","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-03495-z","article-title":"Car-macrophage therapy for her2-overexpressing advanced solid tumors: a phase 1 trial","volume":"31","author":"Reiss","year":"2025","journal-title":"Nat Med"},{"key":"B308","doi-asserted-by":"publisher","DOI":"10.1016\/j.nano.2015.10.012","article-title":"Development of exosome-encapsulated paclitaxel to overcome mdr in cancer cells","volume":"12","author":"Kim","year":"2016","journal-title":"Nanomedicine"},{"key":"B309","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq7248","article-title":"Cancer immunotherapy by gammadelta t cells","volume":"386","author":"Hayday","year":"2024","journal-title":"Science"},{"key":"B310","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.ccell.2020.09.004","article-title":"Immunometabolic interplay in the tumor microenvironment","volume":"39","author":"Kaymak","year":"2021","journal-title":"Cancer Cell"},{"key":"B311","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2020.03.017","article-title":"Acquired resistance to immune checkpoint inhibitors","volume":"37","author":"Schoenfeld","year":"2020","journal-title":"Cancer Cell"},{"key":"B312","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1126\/science.aaa4971","article-title":"Neoantigens in cancer immunotherapy","volume":"348","author":"Schumacher","year":"2015","journal-title":"Science"},{"key":"B313","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0880-x","article-title":"Bl-8040, a cxcr4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the combat trial","volume":"26","author":"Bockorny","year":"2020","journal-title":"Nat Med"},{"key":"B314","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02347-y","article-title":"Oncolytic dnx-2401 virotherapy plus pembrolizumab in recurrent glioblastoma: a phase 1\/2 trial","volume":"29","author":"Nassiri","year":"2023","journal-title":"Nat Med"},{"key":"B315","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41392-023-01480-x","article-title":"Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets","volume":"8","author":"Yang","year":"2023","journal-title":"Signal Transduct Target Ther"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1810065\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T06:10:55Z","timestamp":1780035055000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1810065\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,29]]},"references-count":315,"alternative-id":["10.3389\/fimmu.2026.1810065"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1810065","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,29]]},"article-number":"1810065"}}