{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T13:18:59Z","timestamp":1793107139324,"version":"4.5.0"},"reference-count":126,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Death Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The tumor-immune response is mobilized to suppress tumorigenesis, while the immune microenvironment and lymph node microenvironment are formed gradually during tumor progression. In fact, tumor surface antigens are not easily recognized by antigen-presenting cells. So it is hard for the immune system to kill the newly formed tumor cells effectively. In a normal immune environment, immune function is always suppressed to maintain the stability of the body, and regulatory T cells play an important role in maintaining immune suppression. However, during tumorigenesis, the suppression of regulatory T cell immune functions is more likely to contribute to tumor cell proliferation and migration leading directly to tumor progression. Therefore, focusing on the role of regulatory T cells in tumor immunity could improve tumor immunotherapy outcomes in the clinic. Regulatory T cells are more mature in hematologic system tumors than in solid tumors. However, there are continuing efforts to apply regulatory T cells for immunotherapy in solid tumors. This review describes the role of regulatory T cells in solid tumor immunotherapy from the perspective of prognosis, immune microenvironment remodeling, and current clinical applications. This summary could help us better understand the mechanisms of regulatory T cells in solid tumor immunotherapy and further expand their clinical application.<\/jats:p>","DOI":"10.1038\/s41419-025-07544-w","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T08:56:36Z","timestamp":1744361796000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Regulatory T cells in solid tumor immunotherapy: effect, mechanism and clinical application"],"prefix":"10.1038","volume":"16","author":[{"given":"Yan","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanqiong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9098-7296","authenticated-orcid":false,"given":"Zhenqiang","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9188-066X","authenticated-orcid":false,"given":"Yichen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5959-0310","authenticated-orcid":false,"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3217-1077","authenticated-orcid":false,"given":"Qiming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"7544_CR1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41568-018-0081-9","volume":"19","author":"NK Altorki","year":"2019","unstructured":"Altorki NK, Markowitz GJ, Gao D, Port JL, Saxena A, Stiles B, et al. The lung microenvironment: an important regulator of tumour growth and metastasis. Nat Rev Cancer. 2019;19:9\u201331.","journal-title":"Nat Rev Cancer"},{"key":"7544_CR2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.immuni.2013.07.012","volume":"39","author":"DS Chen","year":"2013","unstructured":"Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39:1\u201310.","journal-title":"Immunity"},{"key":"7544_CR3","unstructured":"\u5434\u601d\u96ef, \u5218\u5b9d\u745e. \u7cbe\u51c6\u80bf\u7624\u533b\u5b66\u4e4b\u5b9e\u8df5: \u9776\u5411\u80bf\u7624\u514d\u75ab\u5fae\u73af\u5883. \u4e2d\u56fd\u80bf\u7624\u751f\u7269\u6cbb\u7597\u6742\u5fd7. 2021;28:769-74."},{"key":"7544_CR4","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s12967-017-1182-z","volume":"15","author":"A Schiza","year":"2017","unstructured":"Schiza A, Wenthe J, Mangsbo S, Eriksson E, Nilsson A, Totterman TH, et al. Adenovirus-mediated CD40L gene transfer increases Teffector\/Tregulatory cell ratio and upregulates death receptors in metastatic melanoma patients. J Transl Med. 2017;15:79.","journal-title":"J Transl Med"},{"key":"7544_CR5","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1053\/j.gastro.2021.06.073","volume":"161","author":"J Gebert","year":"2021","unstructured":"Gebert J, Gelincik O, Oezcan-Wahlbrink M, Marshall JD, Hernandez-Sanchez A, Urban K, et al. Recurrent Frameshift Neoantigen Vaccine Elicits Protective Immunity With Reduced Tumor Burden and Improved Overall Survival in a Lynch Syndrome Mouse Model. Gastroenterology. 2021;161:1288\u2013302.e13.","journal-title":"Gastroenterology"},{"key":"7544_CR6","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1007\/s13238-020-00694-x","volume":"11","author":"X Wang","year":"2020","unstructured":"Wang X, Waschke BC, Woolaver RA, Chen SMY, Chen Z, Wang JH. HDAC inhibitors overcome immunotherapy resistance in B-cell lymphoma. Protein Cell. 2020;11:472\u201382.","journal-title":"Protein Cell"},{"key":"7544_CR7","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/ni.2554","volume":"14","author":"AK Abbas","year":"2013","unstructured":"Abbas AK, Benoist C, Bluestone JA, Campbell DJ, Ghosh S, Hori S, et al. Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol. 2013;14:307\u20138.","journal-title":"Nat Immunol"},{"key":"7544_CR8","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.1111\/febs.13656","volume":"283","author":"C Liu","year":"2016","unstructured":"Liu C, Workman CJ, Vignali DA. Targeting regulatory T cells in tumors. FEBS J. 2016;283:2731\u201348.","journal-title":"FEBS J"},{"key":"7544_CR9","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1158\/2326-6066.CIR-16-0193","volume":"4","author":"G Plitas","year":"2016","unstructured":"Plitas G, Rudensky AY. Regulatory T Cells: Differentiation and Function. Cancer Immunol Res. 2016;4:721\u20135.","journal-title":"Cancer Immunol Res"},{"key":"7544_CR10","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/nm1093","volume":"10","author":"TJ Curiel","year":"2004","unstructured":"Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, et al. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004;10:942\u20139.","journal-title":"Nat Med"},{"key":"7544_CR11","doi-asserted-by":"publisher","first-page":"1467","DOI":"10.1158\/1078-0432.CCR-04-1869","volume":"11","author":"T Alvaro","year":"2005","unstructured":"Alvaro T, Lejeune M, Salvado MT, Bosch R, Garcia JF, Jaen J, et al. Outcome in Hodgkin\u2019s lymphoma can be predicted from the presence of accompanying cytotoxic and regulatory T cells. Clin Cancer Res. 2005;11:1467\u201373.","journal-title":"Clin Cancer Res"},{"key":"7544_CR12","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S0065-230X(10)07003-X","volume":"107","author":"D Mougiakakos","year":"2010","unstructured":"Mougiakakos D, Choudhury A, Lladser A, Kiessling R, Johansson CC. Regulatory T cells in cancer. Adv Cancer Res. 2010;107:57\u2013117.","journal-title":"Adv Cancer Res"},{"key":"7544_CR13","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/cr.2016.151","volume":"27","author":"A Tanaka","year":"2017","unstructured":"Tanaka A, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Cell Res. 2017;27:109\u201318.","journal-title":"Cell Res"},{"key":"7544_CR14","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1189\/jlb.5VMR1116-493R","volume":"102","author":"A Hatziioannou","year":"2017","unstructured":"Hatziioannou A, Alissafi T, Verginis P. Myeloid-derived suppressor cells and T regulatory cells in tumors: unraveling the dark side of the force. J Leukoc Biol. 2017;102:407\u201321.","journal-title":"J Leukoc Biol"},{"key":"7544_CR15","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1111\/j.1600-065X.2012.01148.x","volume":"249","author":"DR Wahl","year":"2012","unstructured":"Wahl DR, Byersdorfer CA, Ferrara JL, Opipari AW Jr, Glick GD. Distinct metabolic programs in activated T cells: opportunities for selective immunomodulation. Immunol Rev. 2012;249:104\u201315.","journal-title":"Immunol Rev"},{"key":"7544_CR16","first-page":"222","volume":"45","author":"C Sakai","year":"2018","unstructured":"Sakai C, Nishikawa H. [Immunosuppressive Environment in Tumors]. Gan Kagaku Ryoho. 2018;45:222\u20136.","journal-title":"Gan Kagaku Ryoho"},{"key":"7544_CR17","doi-asserted-by":"publisher","first-page":"4609","DOI":"10.1200\/JCO.2010.30.5474","volume":"28","author":"FM Johnson","year":"2010","unstructured":"Johnson FM, Bekele BN, Feng L, Wistuba I, Tang XM, Tran HT, et al. Phase II study of dasatinib in patients with advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:4609\u201315.","journal-title":"J Clin Oncol"},{"key":"7544_CR18","doi-asserted-by":"crossref","unstructured":"Redin E, Garmendia I, Lozano T, Serrano D, Senent Y, Redrado M, et al. SRC family kinase (SFK) inhibitor dasatinib improves the antitumor activity of anti-PD-1 in NSCLC models by inhibiting Treg cell conversion and proliferation. J Immunother Cancer. 2021;9:e001496.","DOI":"10.1136\/jitc-2020-001496"},{"key":"7544_CR19","doi-asserted-by":"publisher","first-page":"15179","DOI":"10.1038\/srep15179","volume":"5","author":"B Shang","year":"2015","unstructured":"Shang B, Liu Y, Jiang SJ, Liu Y. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis. Sci Rep. 2015;5:15179.","journal-title":"Sci Rep."},{"key":"7544_CR20","doi-asserted-by":"publisher","first-page":"4089","DOI":"10.1158\/1078-0432.CCR-20-4394","volume":"27","author":"CM Laumont","year":"2021","unstructured":"Laumont CM, Wouters MCA, Smazynski J, Gierc NS, Chavez EA, Chong LC, et al. Single-cell Profiles and Prognostic Impact of Tumor-Infiltrating Lymphocytes Coexpressing CD39, CD103, and PD-1 in Ovarian Cancer. Clin Cancer Res. 2021;27:4089\u2013100.","journal-title":"Clin Cancer Res"},{"key":"7544_CR21","doi-asserted-by":"publisher","first-page":"5685","DOI":"10.1158\/1078-0432.CCR-18-0554","volume":"24","author":"A Toker","year":"2018","unstructured":"Toker A, Nguyen LT, Stone SC, Yang SYC, Katz SR, Shaw PA, et al. Regulatory T Cells in Ovarian Cancer Are Characterized by a Highly Activated Phenotype Distinct from that in Melanoma. Clin Cancer Res. 2018;24:5685\u201396.","journal-title":"Clin Cancer Res"},{"key":"7544_CR22","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1016\/j.immuni.2016.10.021","volume":"45","author":"M De Simone","year":"2016","unstructured":"De Simone M, Arrigoni A, Rossetti G, Gruarin P, Ranzani V, Politano C, et al. Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells. Immunity. 2016;45:1135\u201347.","journal-title":"Immunity"},{"key":"7544_CR23","doi-asserted-by":"publisher","first-page":"4327","DOI":"10.1158\/1078-0432.CCR-15-0357","volume":"21","author":"K Kurose","year":"2015","unstructured":"Kurose K, Ohue Y, Wada H, Iida S, Ishida T, Kojima T, et al. Phase Ia Study of FoxP3+ CD4 Treg Depletion by Infusion of a Humanized Anti-CCR4 Antibody, KW-0761, in Cancer Patients.Clin Cancer Res. 2015;21:4327\u201336.","journal-title":"Clin Cancer Res"},{"key":"7544_CR24","doi-asserted-by":"publisher","first-page":"17945","DOI":"10.1073\/pnas.1316796110","volume":"110","author":"D Sugiyama","year":"2013","unstructured":"Sugiyama D, Nishikawa H, Maeda Y, Nishioka M, Tanemura A, Katayama I, et al. Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans. Proc Natl Acad Sci USA. 2013;110:17945\u201350.","journal-title":"Proc Natl Acad Sci USA"},{"key":"7544_CR25","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.coi.2007.02.004","volume":"19","author":"HY Wang","year":"2007","unstructured":"Wang HY, Wang RF. Regulatory T cells and cancer. Curr Opin Immunol. 2007;19:217\u201323.","journal-title":"Curr Opin Immunol"},{"key":"7544_CR26","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1034\/j.1600-065X.2001.1820116.x","volume":"182","author":"R Cortesini","year":"2001","unstructured":"Cortesini R, LeMaoult J, Ciubotariu R, Cortesini NS. CD8+CD28- T suppressor cells and the induction of antigen-specific, antigen-presenting cell-mediated suppression of Th reactivity. Immunol Rev. 2001;182:201\u20136.","journal-title":"Immunol Rev"},{"key":"7544_CR27","doi-asserted-by":"publisher","first-page":"716559","DOI":"10.3389\/fimmu.2021.716559","volume":"12","author":"MG Aly","year":"2021","unstructured":"Aly MG, Ibrahim EH, Karakizlis H, Weimer R, Opelz G, Morath C, et al. CD4+CD25+CD127-Foxp3+ and CD8+CD28- Tregs in Renal Transplant Recipients: Phenotypic Patterns, Association With Immunosuppressive Drugs, and Interaction With Effector CD8+ T Cells and CD19+IL-10+ Bregs. Front Immunol. 2021;12:716559.","journal-title":"Front Immunol"},{"key":"7544_CR28","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.intimp.2004.09.003","volume":"5","author":"N Suciu-Foca","year":"2005","unstructured":"Suciu-Foca N, Manavalan JS, Scotto L, Kim-Schulze S, Galluzzo S, Naiyer AJ, et al. Molecular characterization of allospecific T suppressor and tolerogenic dendritic cells: review. Int Immunopharmacol. 2005;5:7\u201311.","journal-title":"Int Immunopharmacol"},{"key":"7544_CR29","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.cellimm.2007.01.013","volume":"248","author":"N Suciu-Foca","year":"2007","unstructured":"Suciu-Foca N, Cortesini R. Central role of ILT3 in the T suppressor cell cascade. Cell Immunol. 2007;248:59\u201367.","journal-title":"Cell Immunol"},{"key":"7544_CR30","doi-asserted-by":"publisher","first-page":"4323","DOI":"10.4049\/jimmunol.179.7.4323","volume":"179","author":"G Filaci","year":"2007","unstructured":"Filaci G, Fenoglio D, Fravega M, Ansaldo G, Borgonovo G, Traverso P, et al. CD8+ CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers. J Immunol. 2007;179:4323\u201334.","journal-title":"J Immunol"},{"key":"7544_CR31","doi-asserted-by":"publisher","first-page":"6947","DOI":"10.1158\/1078-0432.CCR-07-0842","volume":"13","author":"Y Kiniwa","year":"2007","unstructured":"Kiniwa Y, Miyahara Y, Wang HY, Peng W, Peng G, Wheeler TM, et al. CD8+ Foxp3+ regulatory T cells mediate immunosuppression in prostate cancer. Clin Cancer Res. 2007;13:6947\u201358.","journal-title":"Clin Cancer Res"},{"key":"7544_CR32","doi-asserted-by":"publisher","first-page":"8029","DOI":"10.1073\/pnas.0702257104","volume":"104","author":"SA Joosten","year":"2007","unstructured":"Joosten SA, van Meijgaarden KE, Savage ND, de Boer T, Triebel F, van der Wal A, et al. Identification of a human CD8+ regulatory T cell subset that mediates suppression through the chemokine CC chemokine ligand 4. Proc Natl Acad Sci USA. 2007;104:8029\u201334.","journal-title":"Proc Natl Acad Sci USA"},{"key":"7544_CR33","doi-asserted-by":"publisher","first-page":"4107","DOI":"10.1182\/blood-2003-04-1320","volume":"102","author":"L Cosmi","year":"2003","unstructured":"Cosmi L, Liotta F, Lazzeri E, Francalanci M, Angeli R, Mazzinghi B, et al. Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes. Blood. 2003;102:4107\u201314.","journal-title":"Blood"},{"key":"7544_CR34","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1182\/blood-2006-02-002774","volume":"108","author":"M Beyer","year":"2006","unstructured":"Beyer M, Schultze JL. Regulatory T cells in cancer. Blood. 2006;108:804\u201311.","journal-title":"Blood"},{"key":"7544_CR35","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.humimm.2008.02.005","volume":"69","author":"SJ Piersma","year":"2008","unstructured":"Piersma SJ, Welters MJ, van der Burg SH. Tumor-specific regulatory T cells in cancer patients. Hum Immunol. 2008;69:241\u20139.","journal-title":"Hum Immunol"},{"key":"7544_CR36","doi-asserted-by":"publisher","first-page":"896","DOI":"10.4049\/jimmunol.177.2.896","volume":"177","author":"AG Jarnicki","year":"2006","unstructured":"Jarnicki AG, Lysaght J, Todryk S, Mills KH. Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells. J Immunol. 2006;177:896\u2013904.","journal-title":"J Immunol"},{"key":"7544_CR37","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.humimm.2008.08.276","volume":"69","author":"RF Wang","year":"2008","unstructured":"Wang RF. CD8+ regulatory T cells, their suppressive mechanisms, and regulation in cancer. Hum Immunol. 2008;69:811\u20134.","journal-title":"Hum Immunol"},{"key":"7544_CR38","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.immuni.2010.08.004","volume":"33","author":"TR Malek","year":"2010","unstructured":"Malek TR, Castro I. Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity. 2010;33:153\u201365.","journal-title":"Immunity"},{"key":"7544_CR39","doi-asserted-by":"crossref","unstructured":"Noyes D, Bag A, Oseni S, Semidey-Hurtado J, Cen L, Sarnaik AA, et al. Tumor-associated Tregs obstruct antitumor immunity by promoting T cell dysfunction and restricting clonal diversity in tumor-infiltrating CD8+ T cells. J Immunother Cancer. 2022;10:e004605.","DOI":"10.1136\/jitc-2022-004605"},{"key":"7544_CR40","doi-asserted-by":"publisher","first-page":"64390","DOI":"10.18632\/oncotarget.10453","volume":"7","author":"A Ray","year":"2016","unstructured":"Ray A, Williams MA, Meek SM, Bowen RC, Grossmann KF, Andtbacka RH, et al. A phase I study of intratumoral ipilimumab and interleukin-2 in patients with advanced melanoma. Oncotarget. 2016;7:64390\u20139.","journal-title":"Oncotarget"},{"key":"7544_CR41","doi-asserted-by":"publisher","first-page":"6389","DOI":"10.1073\/pnas.85.17.6389","volume":"85","author":"GP Dotto","year":"1988","unstructured":"Dotto GP, Weinberg RA, Ariza A. Malignant transformation of mouse primary keratinocytes by Harvey sarcoma virus and its modulation by surrounding normal cells. Proc Natl Acad Sci USA. 1988;85:6389\u201393.","journal-title":"Proc Natl Acad Sci USA"},{"key":"7544_CR42","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1101\/gad.279737.116","volume":"30","author":"P Gascard","year":"2016","unstructured":"Gascard P, Tlsty TD. Carcinoma-associated fibroblasts: orchestrating the composition of malignancy. Genes Dev. 2016;30:1002\u201319.","journal-title":"Genes Dev"},{"key":"7544_CR43","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1089\/ars.2016.6750","volume":"26","author":"G Gentric","year":"2017","unstructured":"Gentric G, Mieulet V, Mechta-Grigoriou F. Heterogeneity in Cancer Metabolism: New Concepts in an Old Field. Antioxid Redox Signal. 2017;26:462\u201385.","journal-title":"Antioxid Redox Signal"},{"key":"7544_CR44","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1038\/nature11183","volume":"487","author":"R Straussman","year":"2012","unstructured":"Straussman R, Morikawa T, Shee K, Barzily-Rokni M, Qian ZR, Du J, et al. Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature. 2012;487:500\u20134.","journal-title":"Nature"},{"key":"7544_CR45","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1002\/cjp2.56","volume":"3","author":"J Paulsson","year":"2017","unstructured":"Paulsson J, Ryden L, Strell C, Frings O, Tobin NP, Fornander T, et al. High expression of stromal PDGFRbeta is associated with reduced benefit of tamoxifen in breast cancer. J Pathol Clin Res. 2017;3:38\u201343.","journal-title":"J Pathol Clin Res"},{"key":"7544_CR46","doi-asserted-by":"publisher","first-page":"4124","DOI":"10.1158\/0008-5472.CAN-15-2973","volume":"76","author":"X Yang","year":"2016","unstructured":"Yang X, Lin Y, Shi Y, Li B, Liu W, Yin W, et al. FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3-CCL2 Signaling. Cancer Res. 2016;76:4124\u201335.","journal-title":"Cancer Res"},{"key":"7544_CR47","doi-asserted-by":"publisher","first-page":"11762","DOI":"10.1038\/ncomms11762","volume":"7","author":"MK Ruhland","year":"2016","unstructured":"Ruhland MK, Loza AJ, Capietto AH, Luo X, Knolhoff BL, Flanagan KC, et al. Stromal senescence establishes an immunosuppressive microenvironment that drives tumorigenesis. Nat Commun. 2016;7:11762.","journal-title":"Nat Commun"},{"key":"7544_CR48","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/nrc.2017.117","volume":"18","author":"S Spranger","year":"2018","unstructured":"Spranger S, Gajewski TF. Impact of oncogenic pathways on evasion of antitumour immune responses. Nat Rev Cancer. 2018;18:139\u201347.","journal-title":"Nat Rev Cancer"},{"key":"7544_CR49","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/nature06306","volume":"450","author":"LW Collison","year":"2007","unstructured":"Collison LW, Workman CJ, Kuo TT, Boyd K, Wang Y, Vignali KM, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature. 2007;450:566\u20139.","journal-title":"Nature"},{"key":"7544_CR50","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.ccell.2022.04.011","volume":"40","author":"H Huang","year":"2022","unstructured":"Huang H, Wang Z, Zhang Y, Pradhan RN, Ganguly D, Chandra R, et al. Mesothelial cell-derived antigen-presenting cancer-associated fibroblasts induce expansion of regulatory T cells in pancreatic cancer. Cancer Cell. 2022;40:656\u201373.e7.","journal-title":"Cancer Cell"},{"key":"7544_CR51","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.cell.2015.03.045","volume":"161","author":"SL Topalian","year":"2015","unstructured":"Topalian SL, Wolchok JD, Chan TA, Mellman I, Palucka K, Banchereau J, et al. Immunotherapy: The path to win the war on cancer? Cell. 2015;161:185\u20136.","journal-title":"Cell"},{"key":"7544_CR52","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","volume":"168","author":"P Sharma","year":"2017","unstructured":"Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017;168:707\u201323.","journal-title":"Cell"},{"key":"7544_CR53","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nrclinonc.2018.29","volume":"15","author":"D Fukumura","year":"2018","unstructured":"Fukumura D, Kloepper J, Amoozgar Z, Duda DG, Jain RK. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat Rev Clin Oncol. 2018;15:325\u201340.","journal-title":"Nat Rev Clin Oncol"},{"key":"7544_CR54","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1084\/jem.20041982","volume":"201","author":"R Setoguchi","year":"2005","unstructured":"Setoguchi R, Hori S, Takahashi T, Sakaguchi S. Homeostatic maintenance of natural Foxp3(+) CD25(+) CD4(+) regulatory T cells by interleukin (IL)-2 and induction of autoimmune disease by IL-2 neutralization. J Exp Med. 2005;201:723\u201335.","journal-title":"J Exp Med"},{"key":"7544_CR55","first-page":"823","volume":"33","author":"M Janke","year":"2008","unstructured":"Janke M, Peeters B, Zhao H, de Leeuw O, Moorman R, Arnold A, et al. Activation of human T cells by a tumor vaccine infected with recombinant Newcastle disease virus producing IL-2. Int J Oncol. 2008;33:823\u201332.","journal-title":"Int J Oncol"},{"key":"7544_CR56","doi-asserted-by":"publisher","first-page":"2840","DOI":"10.1182\/blood-2004-03-0859","volume":"104","author":"WJ Grossman","year":"2004","unstructured":"Grossman WJ, Verbsky JW, Tollefsen BL, Kemper C, Atkinson JP, Ley TJ. Differential expression of granzymes A and B in human cytotoxic lymphocyte subsets and T regulatory cells. Blood. 2004;104:2840\u20138.","journal-title":"Blood"},{"key":"7544_CR57","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/mi.2011.62","volume":"5","author":"J Loebbermann","year":"2012","unstructured":"Loebbermann J, Thornton H, Durant L, Sparwasser T, Webster KE, Sprent J, et al. Regulatory T cells expressing granzyme B play a critical role in controlling lung inflammation during acute viral infection. Mucosal Immunol. 2012;5:161\u201372.","journal-title":"Mucosal Immunol"},{"key":"7544_CR58","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/nri3108","volume":"11","author":"LS Walker","year":"2011","unstructured":"Walker LS, Sansom DM. The emerging role of CTLA4 as a cell-extrinsic regulator of T cell responses. Nat Rev Immunol. 2011;11:852\u201363.","journal-title":"Nat Rev Immunol"},{"key":"7544_CR59","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1111\/cas.14069","volume":"110","author":"Y Ohue","year":"2019","unstructured":"Ohue Y, Nishikawa H. Regulatory T (Treg) cells in cancer: Can Treg cells be a new therapeutic target?. Cancer Sci. 2019;110:2080\u20139.","journal-title":"Cancer Sci"},{"key":"7544_CR60","doi-asserted-by":"crossref","unstructured":"Koido S. Dendritic-Tumor Fusion Cell-Based Cancer Vaccines. Int J Mol Sci. 2016;17:828.","DOI":"10.3390\/ijms17060828"},{"key":"7544_CR61","doi-asserted-by":"publisher","first-page":"1695","DOI":"10.1084\/jem.20130579","volume":"210","author":"TR Simpson","year":"2013","unstructured":"Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K, Arce F, et al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med. 2013;210:1695\u2013710.","journal-title":"J Exp Med"},{"key":"7544_CR62","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1038\/nm934","volume":"9","author":"C Uyttenhove","year":"2003","unstructured":"Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, et al. Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med. 2003;9:1269\u201374.","journal-title":"Nat Med"},{"key":"7544_CR63","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1038\/nri1457","volume":"4","author":"AL Mellor","year":"2004","unstructured":"Mellor AL, Munn DH. IDO expression by dendritic cells: tolerance and tryptophan catabolism. Nat Rev Immunol. 2004;4:762\u201374.","journal-title":"Nat Rev Immunol"},{"key":"7544_CR64","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/nature21349","volume":"541","author":"DS Chen","year":"2017","unstructured":"Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321\u201330.","journal-title":"Nature"},{"key":"7544_CR65","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/nri1806","volume":"6","author":"W Zou","year":"2006","unstructured":"Zou W. Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol. 2006;6:295\u2013307.","journal-title":"Nat Rev Immunol"},{"key":"7544_CR66","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.immuni.2009.04.010","volume":"30","author":"EM Shevach","year":"2009","unstructured":"Shevach EM. Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity. 2009;30:636\u201345.","journal-title":"Immunity"},{"key":"7544_CR67","doi-asserted-by":"publisher","first-page":"7983","DOI":"10.1002\/jcp.27553","volume":"234","author":"M Najafi","year":"2019","unstructured":"Najafi M, Farhood B, Mortezaee K. Contribution of regulatory T cells to cancer: A review. J Cell Physiol. 2019;234:7983\u201393.","journal-title":"J Cell Physiol"},{"key":"7544_CR68","doi-asserted-by":"publisher","first-page":"6915","DOI":"10.1158\/0008-5472.CAN-11-1156","volume":"71","author":"WL Byrne","year":"2011","unstructured":"Byrne WL, Mills KH, Lederer JA, O\u2019Sullivan GC. Targeting regulatory T cells in cancer. Cancer Res. 2011;71:6915\u201320.","journal-title":"Cancer Res"},{"key":"7544_CR69","doi-asserted-by":"publisher","first-page":"3783","DOI":"10.4049\/jimmunol.1201449","volume":"190","author":"J Yu","year":"2013","unstructured":"Yu J, Du W, Yan F, Wang Y, Li H, Cao S, et al. Myeloid-derived suppressor cells suppress antitumor immune responses through IDO expression and correlate with lymph node metastasis in patients with breast cancer. J Immunol. 2013;190:3783\u201397.","journal-title":"J Immunol"},{"key":"7544_CR70","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1007\/s00262-011-1178-0","volume":"61","author":"MR Porembka","year":"2012","unstructured":"Porembka MR, Mitchem JB, Belt BA, Hsieh CS, Lee HM, Herndon J, et al. Pancreatic adenocarcinoma induces bone marrow mobilization of myeloid-derived suppressor cells which promote primary tumor growth. Cancer Immunol Immunother. 2012;61:1373\u201385.","journal-title":"Cancer Immunol Immunother"},{"key":"7544_CR71","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1007\/s11060-015-1720-6","volume":"122","author":"B Raychaudhuri","year":"2015","unstructured":"Raychaudhuri B, Rayman P, Huang P, Grabowski M, Hambardzumyan D, Finke JH, et al. Myeloid derived suppressor cell infiltration of murine and human gliomas is associated with reduction of tumor infiltrating lymphocytes. J Neuro Oncol. 2015;122:293\u2013301.","journal-title":"J Neuro Oncol"},{"key":"7544_CR72","doi-asserted-by":"publisher","first-page":"3365","DOI":"10.1172\/JCI80006","volume":"125","author":"S Ugel","year":"2015","unstructured":"Ugel S, De Sanctis F, Mandruzzato S, Bronte V. Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages. J Clin Invest. 2015;125:3365\u201376.","journal-title":"J Clin Invest"},{"key":"7544_CR73","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1016\/j.it.2016.01.004","volume":"37","author":"V Kumar","year":"2016","unstructured":"Kumar V, Patel S, Tcyganov E, Gabrilovich DI. The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment. Trends Immunol. 2016;37:208\u201320.","journal-title":"Trends Immunol"},{"key":"7544_CR74","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1016\/j.cell.2017.05.005","volume":"169","author":"AE Overacre-Delgoffe","year":"2017","unstructured":"Overacre-Delgoffe AE, Chikina M, Dadey RE, Yano H, Brunazzi EA, Shayan G, et al. Interferon-gamma Drives T(reg) Fragility to Promote Anti-tumor Immunity. Cell. 2017;169:1130\u201341.e11.","journal-title":"Cell"},{"key":"7544_CR75","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.immuni.2019.06.017","volume":"51","author":"C Liu","year":"2019","unstructured":"Liu C, Chikina M, Deshpande R, Menk AV, Wang T, Tabib T, et al. Treg Cells Promote the SREBP1-Dependent Metabolic Fitness of Tumor-Promoting Macrophages via Repression of CD8(+) T Cell-Derived Interferon-gamma. Immunity. 2019;51:381\u201397.e6.","journal-title":"Immunity"},{"key":"7544_CR76","doi-asserted-by":"crossref","unstructured":"Atri C, Guerfali FZ, Laouini D. Role of Human Macrophage Polarization in Inflammation during Infectious Diseases. Int J Mol Sci. 2018;19:1801.","DOI":"10.3390\/ijms19061801"},{"key":"7544_CR77","doi-asserted-by":"publisher","first-page":"514","DOI":"10.3389\/fimmu.2014.00514","volume":"5","author":"P Italiani","year":"2014","unstructured":"Italiani P, Boraschi D. From Monocytes to M1\/M2 Macrophages: Phenotypical vs. Functional Differentiation. Front Immunol. 2014;5:514.","journal-title":"Front Immunol"},{"key":"7544_CR78","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1111\/imr.12758","volume":"289","author":"B Leon","year":"2019","unstructured":"Leon B, Lund FE. Compartmentalization of dendritic cell and T-cell interactions in the lymph node: Anatomy of T-cell fate decisions. Immunol Rev. 2019;289:84\u2013100.","journal-title":"Immunol Rev"},{"key":"7544_CR79","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1002\/med.21855","volume":"42","author":"S Rezzola","year":"2022","unstructured":"Rezzola S, Sigmund EC, Halin C, Ronca R. The lymphatic vasculature: An active and dynamic player in cancer progression. Med Res Rev. 2022;42:576\u2013614.","journal-title":"Med Res Rev"},{"key":"7544_CR80","doi-asserted-by":"publisher","first-page":"4110","DOI":"10.1016\/j.celrep.2020.03.007","volume":"30","author":"R Nadafi","year":"2020","unstructured":"Nadafi R, Gago de Graca C, Keuning ED, Koning JJ, de Kivit S, Konijn T, et al. Lymph Node Stromal Cells Generate Antigen-Specific Regulatory T Cells and Control Autoreactive T and B Cell Responses. Cell Rep. 2020;30:4110\u201323.e4.","journal-title":"Cell Rep."},{"key":"7544_CR81","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1038\/s41568-019-0221-x","volume":"20","author":"G Follain","year":"2020","unstructured":"Follain G, Herrmann D, Harlepp S, Hyenne V, Osmani N, Warren SC, et al. Fluids and their mechanics in tumour transit: shaping metastasis. Nat Rev Cancer. 2020;20:107\u201324.","journal-title":"Nat Rev Cancer"},{"key":"7544_CR82","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1126\/science.aav0173","volume":"363","author":"CK Lee","year":"2019","unstructured":"Lee CK, Jeong SH, Jang C, Bae H, Kim YH, Park I, et al. Tumor metastasis to lymph nodes requires YAP-dependent metabolic adaptation. Science. 2019;363:644\u20139.","journal-title":"Science"},{"key":"7544_CR83","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1158\/1078-0432.CCR-14-1860","volume":"21","author":"GL Beatty","year":"2015","unstructured":"Beatty GL, Gladney WL. Immune escape mechanisms as a guide for cancer immunotherapy. Clin Cancer Res. 2015;21:687\u201392.","journal-title":"Clin Cancer Res"},{"key":"7544_CR84","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/j.it.2016.09.006","volume":"37","author":"A Gardner","year":"2016","unstructured":"Gardner A, Ruffell B. Dendritic Cells and Cancer Immunity. Trends Immunol. 2016;37:855\u201365.","journal-title":"Trends Immunol"},{"key":"7544_CR85","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1038\/ni.2112","volume":"12","author":"V Lukacs-Kornek","year":"2011","unstructured":"Lukacs-Kornek V, Malhotra D, Fletcher AL, Acton SE, Elpek KG, Tayalia P, et al. Regulated release of nitric oxide by nonhematopoietic stroma controls expansion of the activated T cell pool in lymph nodes. Nat Immunol. 2011;12:1096\u2013104.","journal-title":"Nat Immunol"},{"key":"7544_CR86","doi-asserted-by":"publisher","first-page":"15478","DOI":"10.1073\/pnas.0703725104","volume":"104","author":"W Niedbala","year":"2007","unstructured":"Niedbala W, Cai B, Liu H, Pitman N, Chang L, Liew FY. Nitric oxide induces CD4+CD25+ Foxp3 regulatory T cells from CD4+CD25 T cells via p53, IL-2, and OX40. Proc Natl Acad Sci USA. 2007;104:15478\u201383.","journal-title":"Proc Natl Acad Sci USA"},{"key":"7544_CR87","unstructured":"\u300a\u4e2d\u56fd\u80bf\u7624\u4e34\u5e8a\u300b\u6587\u7ae0\u63a8\u8350: Bcl-2\u6291\u5236\u5242\u5728\u6dcb\u5df4\u80bf\u7624\u6cbb\u7597\u4e2d\u7684\u5e94\u7528. \u4e2d\u56fd\u80bf\u7624\u4e34\u5e8a. 2021;48:819."},{"key":"7544_CR88","doi-asserted-by":"publisher","first-page":"2622","DOI":"10.4049\/jimmunol.1301369","volume":"192","author":"PS Kim","year":"2014","unstructured":"Kim PS, Jochems C, Grenga I, Donahue RN, Tsang KY, Gulley JL, et al. Pan-Bcl-2 inhibitor, GX15-070 (obatoclax), decreases human T regulatory lymphocytes while preserving effector T lymphocytes: a rationale for its use in combination immunotherapy. J Immunol. 2014;192:2622\u201333.","journal-title":"J Immunol"},{"key":"7544_CR89","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1002\/ijc.25177","volume":"127","author":"B Farsaci","year":"2010","unstructured":"Farsaci B, Sabzevari H, Higgins JP, Di Bari MG, Takai S, Schlom J, et al. Effect of a small molecule BCL-2 inhibitor on immune function and use with a recombinant vaccine. Int J Cancer. 2010;127:1603\u201313.","journal-title":"Int J Cancer"},{"key":"7544_CR90","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.clim.2009.10.005","volume":"134","author":"XL Yuan","year":"2010","unstructured":"Yuan XL, Chen L, Li MX, Dong P, Xue J, Wang J, et al. Elevated expression of Foxp3 in tumor-infiltrating Treg cells suppresses T-cell proliferation and contributes to gastric cancer progression in a COX-2-dependent manner. Clin Immunol. 2010;134:277\u201388.","journal-title":"Clin Immunol"},{"key":"7544_CR91","doi-asserted-by":"publisher","first-page":"1875","DOI":"10.1016\/j.ejca.2008.05.017","volume":"44","author":"G Perrone","year":"2008","unstructured":"Perrone G, Ruffini PA, Catalano V, Spino C, Santini D, Muretto P, et al. Intratumoural FOXP3-positive regulatory T cells are associated with adverse prognosis in radically resected gastric cancer. Eur J Cancer. 2008;44:1875\u201382.","journal-title":"Eur J Cancer"},{"key":"7544_CR92","doi-asserted-by":"publisher","first-page":"e63777","DOI":"10.1371\/journal.pone.0063777","volume":"8","author":"B Deng","year":"2013","unstructured":"Deng B, Zhu JM, Wang Y, Liu TT, Ding YB, Xiao WM, et al. Intratumor hypoxia promotes immune tolerance by inducing regulatory T cells via TGF-beta1 in gastric cancer. PLoS One. 2013;8:e63777.","journal-title":"PLoS One"},{"key":"7544_CR93","doi-asserted-by":"publisher","first-page":"e16195","DOI":"10.1371\/journal.pone.0016195","volume":"6","author":"J Wei","year":"2011","unstructured":"Wei J, Wu A, Kong LY, Wang Y, Fuller G, Fokt I, et al. Hypoxia potentiates glioma-mediated immunosuppression. PLoS One. 2011;6:e16195.","journal-title":"PLoS One"},{"key":"7544_CR94","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1007\/s00109-007-0281-3","volume":"85","author":"MC Brahimi-Horn","year":"2007","unstructured":"Brahimi-Horn MC, Chiche J, Pouyssegur J. Hypoxia and cancer. J Mol Med (Berl). 2007;85:1301\u20137.","journal-title":"J Mol Med (Berl)"},{"key":"7544_CR95","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/s41408-021-00514-3","volume":"11","author":"M Yilmaz","year":"2021","unstructured":"Yilmaz M, Kantarjian H, Ravandi F. Acute promyelocytic leukemia current treatment algorithms. Blood Cancer J. 2021;11:123.","journal-title":"Blood Cancer J"},{"key":"7544_CR96","doi-asserted-by":"publisher","first-page":"5191","DOI":"10.7314\/APJCP.2015.16.13.5191","volume":"16","author":"TO Bakhshaiesh","year":"2015","unstructured":"Bakhshaiesh TO, Armat M, Shanehbandi D, Sharifi S, Baradaran B, Hejazi MS, et al. Arsenic Trioxide Promotes Paclitaxel Cytotoxicity in Resistant Breast Cancer Cells. Asian Pac J Cancer Prev. 2015;16:5191\u20137.","journal-title":"Asian Pac J Cancer Prev"},{"key":"7544_CR97","doi-asserted-by":"publisher","first-page":"3243","DOI":"10.3892\/ol.2017.6502","volume":"14","author":"Y Jian","year":"2017","unstructured":"Jian Y, Gao W, Geng C, Zhou H, Leng Y, Li Y, et al. Arsenic trioxide potentiates sensitivity of multiple myeloma cells to lenalidomide by upregulating cereblon expression levels. Oncol Lett. 2017;14:3243\u20138.","journal-title":"Oncol Lett"},{"key":"7544_CR98","doi-asserted-by":"publisher","first-page":"5171","DOI":"10.4049\/jimmunol.1103094","volume":"189","author":"A Thomas-Schoemann","year":"2012","unstructured":"Thomas-Schoemann A, Batteux F, Mongaret C, Nicco C, Chereau C, Annereau M, et al. Arsenic trioxide exerts antitumor activity through regulatory T cell depletion mediated by oxidative stress in a murine model of colon cancer. J Immunol. 2012;189:5171\u20137.","journal-title":"J Immunol"},{"key":"7544_CR99","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/cgt.2010.21","volume":"17","author":"AS Bergot","year":"2010","unstructured":"Bergot AS, Durgeau A, Levacher B, Colombo BM, Cohen JL, Klatzmann D. Antigen quality determines the efficiency of antitumor immune responses generated in the absence of regulatory T cells. Cancer Gene Ther. 2010;17:645\u201354.","journal-title":"Cancer Gene Ther"},{"key":"7544_CR100","first-page":"1","volume":"2","author":"E Jones","year":"2002","unstructured":"Jones E, Dahm-Vicker M, Simon AK, Green A, Powrie F, Cerundolo V, et al. Depletion of CD25+ regulatory cells results in suppression of melanoma growth and induction of autoreactivity in mice. Cancer Immun. 2002;2:1.","journal-title":"Cancer Immun"},{"key":"7544_CR101","first-page":"8384","volume":"63","author":"J Li","year":"2003","unstructured":"Li J, Hu P, Khawli LA, Epstein AL. Complete regression of experimental solid tumors by combination LEC\/chTNT-3 immunotherapy and CD25(+) T-cell depletion. Cancer Res. 2003;63:8384\u201392.","journal-title":"Cancer Res"},{"key":"7544_CR102","doi-asserted-by":"publisher","first-page":"2665","DOI":"10.1158\/0008-5472.CAN-09-1574","volume":"70","author":"MW Teng","year":"2010","unstructured":"Teng MW, Swann JB, von Scheidt B, Sharkey J, Zerafa N, McLaughlin N, et al. Multiple antitumor mechanisms downstream of prophylactic regulatory T-cell depletion. Cancer Res. 2010;70:2665\u201374.","journal-title":"Cancer Res"},{"key":"7544_CR103","doi-asserted-by":"publisher","first-page":"5067","DOI":"10.1158\/1078-0432.CCR-10-1757","volume":"16","author":"JF Jacobs","year":"2010","unstructured":"Jacobs JF, Punt CJ, Lesterhuis WJ, Sutmuller RP, Brouwer HM, Scharenborg NM, et al. Dendritic cell vaccination in combination with anti-CD25 monoclonal antibody treatment: a phase I\/II study in metastatic melanoma patients. Clin Cancer Res. 2010;16:5067\u201378.","journal-title":"Clin Cancer Res"},{"key":"7544_CR104","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1084\/jem.20050940","volume":"202","author":"K Ko","year":"2005","unstructured":"Ko K, Yamazaki S, Nakamura K, Nishioka T, Hirota K, Yamaguchi T, et al. Treatment of advanced tumors with agonistic anti-GITR mAb and its effects on tumor-infiltrating Foxp3+CD25+CD4+ regulatory T cells. J Exp Med. 2005;202:885\u201391.","journal-title":"J Exp Med"},{"key":"7544_CR105","doi-asserted-by":"publisher","first-page":"2125","DOI":"10.1084\/jem.20080099","volume":"205","author":"SA Quezada","year":"2008","unstructured":"Quezada SA, Peggs KS, Simpson TR, Shen Y, Littman DR, Allison JP. Limited tumor infiltration by activated T effector cells restricts the therapeutic activity of regulatory T cell depletion against established melanoma. J Exp Med. 2008;205:2125\u201338.","journal-title":"J Exp Med"},{"key":"7544_CR106","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1126\/science.aaa4971","volume":"348","author":"TN Schumacher","year":"2015","unstructured":"Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348:69\u201374.","journal-title":"Science"},{"key":"7544_CR107","doi-asserted-by":"publisher","first-page":"1098","DOI":"10.1038\/nm.3317","volume":"19","author":"RH Vonderheide","year":"2013","unstructured":"Vonderheide RH, Nathanson KL. Immunotherapy at large: the road to personalized cancer vaccines. Nat Med. 2013;19:1098\u2013100.","journal-title":"Nat Med"},{"key":"7544_CR108","doi-asserted-by":"publisher","first-page":"e29311","DOI":"10.4161\/onci.29311","volume":"3","author":"EF Fritsch","year":"2014","unstructured":"Fritsch EF, Hacohen N, Wu CJ. Personal neoantigen cancer vaccines: The momentum builds. Oncoimmunology. 2014;3:e29311.","journal-title":"Oncoimmunology"},{"key":"7544_CR109","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1002\/iid3.136","volume":"5","author":"SA Fisher","year":"2017","unstructured":"Fisher SA, Aston WJ, Chee J, Khong A, Cleaver AL, Solin JN, et al. Transient Treg depletion enhances therapeutic anti-cancer vaccination. Immun Inflamm Dis. 2017;5:16\u201328.","journal-title":"Immun Inflamm Dis"},{"key":"7544_CR110","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1007\/s00262-020-02496-w","volume":"69","author":"QT Wang","year":"2020","unstructured":"Wang QT, Nie Y, Sun SN, Lin T, Han RJ, Jiang J, et al. Tumor-associated antigen-based personalized dendritic cell vaccine in solid tumor patients. Cancer Immunol Immunother. 2020;69:1375\u201387.","journal-title":"Cancer Immunol Immunother"},{"key":"7544_CR111","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1158\/1078-0432.CCR-05-1886","volume":"12","author":"C Badoual","year":"2006","unstructured":"Badoual C, Hans S, Rodriguez J, Peyrard S, Klein C, Agueznay Nel H, et al. Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res. 2006;12:465\u201372.","journal-title":"Clin Cancer Res"},{"key":"7544_CR112","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1200\/JCO.2008.18.7229","volume":"27","author":"P Salama","year":"2009","unstructured":"Salama P, Phillips M, Grieu F, Morris M, Zeps N, Joseph D, et al. Tumor-infiltrating FOXP3+ T regulatory cells show strong prognostic significance in colorectal cancer. J Clin Oncol. 2009;27:186\u201392.","journal-title":"J Clin Oncol"},{"key":"7544_CR113","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/bjc.2012.524","volume":"108","author":"NR West","year":"2013","unstructured":"West NR, Kost SE, Martin SD, Milne K, Deleeuw RJ, Nelson BH, et al. Tumour-infiltrating FOXP3(+) lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer. Br J Cancer. 2013;108:155\u201362.","journal-title":"Br J Cancer"},{"key":"7544_CR114","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1007\/s10585-013-9602-9","volume":"30","author":"L Demir","year":"2013","unstructured":"Demir L, Yigit S, Ellidokuz H, Erten C, Somali I, Kucukzeybek Y, et al. Predictive and prognostic factors in locally advanced breast cancer: effect of intratumoral FOXP3+ Tregs. Clin Exp Metastasis. 2013;30:1047\u201362.","journal-title":"Clin Exp Metastasis"},{"key":"7544_CR115","doi-asserted-by":"publisher","first-page":"e6412","DOI":"10.1371\/journal.pone.0006412","volume":"4","author":"K Milne","year":"2009","unstructured":"Milne K, Kobel M, Kalloger SE, Barnes RO, Gao D, Gilks CB, et al. Systematic analysis of immune infiltrates in high-grade serous ovarian cancer reveals CD20, FoxP3 and TIA-1 as positive prognostic factors. PLoS One. 2009;4:e6412.","journal-title":"PLoS One"},{"key":"7544_CR116","doi-asserted-by":"publisher","first-page":"672356","DOI":"10.3389\/fimmu.2021.672356","volume":"12","author":"Z Zhang","year":"2021","unstructured":"Zhang Z, Lu M, Qin Y, Gao W, Tao L, Su W, et al. Neoantigen: A New Breakthrough in Tumor Immunotherapy. Front Immunol. 2021;12:672356.","journal-title":"Front Immunol"},{"key":"7544_CR117","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/s41423-020-0488-6","volume":"17","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, Zhang Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell Mol Immunol. 2020;17:807\u201321.","journal-title":"Cell Mol Immunol"},{"key":"7544_CR118","doi-asserted-by":"publisher","first-page":"212297","DOI":"10.7573\/dic.212297","volume":"5","author":"IS Jensen","year":"2016","unstructured":"Jensen IS, Zacherle E, Blanchette CM, Zhang J, Yin W. Evaluating cost benefits of combination therapies for advanced melanoma. Drugs Context. 2016;5:212297.","journal-title":"Drugs Context"},{"key":"7544_CR119","doi-asserted-by":"publisher","first-page":"23","DOI":"10.2174\/187153007780059432","volume":"7","author":"A Loskog","year":"2007","unstructured":"Loskog A, Totterman TH. CD40L - a multipotent molecule for tumor therapy. Endocr Metab Immune Disord Drug Targets. 2007;7:23\u20138.","journal-title":"Endocr Metab Immune Disord Drug Targets"},{"key":"7544_CR120","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.1158\/1078-0432.CCR-10-0385","volume":"16","author":"PU Malmstrom","year":"2010","unstructured":"Malmstrom PU, Loskog AS, Lindqvist CA, Mangsbo SM, Fransson M, Wanders A, et al. AdCD40L immunogene therapy for bladder carcinoma-the first phase I\/IIa trial. Clin Cancer Res. 2010;16:3279\u201387.","journal-title":"Clin Cancer Res"},{"key":"7544_CR121","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","volume":"133","author":"S Sakaguchi","year":"2008","unstructured":"Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775\u201387.","journal-title":"Cell"},{"key":"7544_CR122","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1097\/CJI.0b013e3181f4c208","volume":"33","author":"O Adotevi","year":"2010","unstructured":"Adotevi O, Pere H, Ravel P, Haicheur N, Badoual C, Merillon N, et al. A decrease of regulatory T cells correlates with overall survival after sunitinib-based antiangiogenic therapy in metastatic renal cancer patients. J Immunother. 2010;33:991\u20138.","journal-title":"J Immunother"},{"key":"7544_CR123","doi-asserted-by":"publisher","first-page":"e2100881","DOI":"10.1002\/advs.202100881","volume":"8","author":"W Xiong","year":"2021","unstructured":"Xiong W, Zhang B, Yu H, Zhu L, Yi L, Jin X. RRM2 Regulates Sensitivity to Sunitinib and PD-1 Blockade in Renal Cancer by Stabilizing ANXA1 and Activating the AKT Pathway. Adv Sci (Weinh). 2021;8:e2100881.","journal-title":"Adv Sci (Weinh)"},{"key":"7544_CR124","doi-asserted-by":"publisher","first-page":"7280","DOI":"10.1038\/s41467-021-27574-0","volume":"12","author":"Y Maeda","year":"2021","unstructured":"Maeda Y, Wada H, Sugiyama D, Saito T, Irie T, Itahashi K, et al. Depletion of central memory CD8(+) T cells might impede the antitumor therapeutic effect of Mogamulizumab. Nat Commun. 2021;12:7280.","journal-title":"Nat Commun"},{"key":"7544_CR125","doi-asserted-by":"publisher","first-page":"2493","DOI":"10.1016\/j.cmet.2024.10.019","volume":"36","author":"H Tong","year":"2024","unstructured":"Tong H, Jiang Z, Song L, Tan K, Yin X, He C, et al. Dual impacts of serine\/glycine-free diet in enhancing antitumor immunity and promoting evasion via PD-L1 lactylation. Cell Metab. 2024;36:2493\u2013510.e9.","journal-title":"Cell Metab"},{"key":"7544_CR126","doi-asserted-by":"publisher","first-page":"4205","DOI":"10.1158\/1078-0432.CCR-20-4862","volume":"27","author":"R Virtakoivu","year":"2021","unstructured":"Virtakoivu R, Rannikko JH, Viitala M, Vaura F, Takeda A, Lonnberg T, et al. Systemic Blockade of Clever-1 Elicits Lymphocyte Activation Alongside Checkpoint Molecule Downregulation in Patients with Solid Tumors: Results from a Phase I\/II Clinical Trial. Clin Cancer Res. 2021;27:4205\u201320.","journal-title":"Clin Cancer Res"}],"container-title":["Cell Death &amp; Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-07544-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-07544-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-07544-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T13:03:45Z","timestamp":1744376625000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41419-025-07544-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,11]]},"references-count":126,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["7544"],"URL":"https:\/\/doi.org\/10.1038\/s41419-025-07544-w","relation":{},"ISSN":["2041-4889"],"issn-type":[{"value":"2041-4889","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,11]]},"assertion":[{"value":"30 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"277"}}