{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:43:54Z","timestamp":1792788234661,"version":"4.5.0"},"reference-count":193,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:00:00Z","timestamp":1791590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Natural Science Foundation of China","award":["No. 82573543"],"award-info":[{"award-number":["No. 82573543"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Original Exploration Project of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine","award":["No. JYYC012"],"award-info":[{"award-number":["No. JYYC012"]}],"id":[{"id":"https:\/\/ror.org\/0220qvk04","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Shanghai Hospital Development Center","award":["SHDC2023CRT009"],"award-info":[{"award-number":["SHDC2023CRT009"]}],"id":[{"id":"https:\/\/ror.org\/02zrtve16","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immune checkpoint blockade (ICB) has reshaped the therapeutic landscape of solid tumors. However, durable clinical benefit remains limited to a subset of patients because of primary or acquired resistance. Beyond tumor-intrinsic factors, the tumor microenvironment (TME) plays a critical role in shaping responsiveness to immunotherapy. As a major stromal component, cancer-associated fibroblasts (CAFs) contribute to immune suppression through dynamic metabolic reprogramming and modulate the spatial organization and functional state of immune cells. Recent advances in single-cell transcriptomics, spatial omics, and metabolomic profiling have provided new insights into the metabolic heterogeneity of CAF subsets and their interactions with immune cells. Metabolic reprogramming not only sustains CAF activation but also remodels the local immune environment through nutrient competition, metabolite accumulation, and coordination with extracellular matrix remodeling. These processes reinforce immunosuppression within the TME and contribute to resistance to ICB. This review integrates emerging multi-omics insights into CAF metabolic heterogeneity, summarizes how metabolic reprogramming shapes tumor immunity, and discusses therapeutic strategies targeting CAF metabolism to enhance immunotherapy efficacy, together with the major challenges facing clinical translation.<\/jats:p>","DOI":"10.1186\/s40164-026-00837-6","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:30:26Z","timestamp":1791667826000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metabolic reprogramming in cancer-associated fibroblasts: orchestrating the tumor immune microenvironment and response to immune checkpoint blockade"],"prefix":"10.1186","volume":"15","author":[{"given":"Luoman","family":"Gan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonglong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liren","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanhao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8839-7767","authenticated-orcid":false,"given":"Yue","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,10]]},"reference":[{"issue":"8","key":"837_CR1","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1016\/j.cell.2023.03.006","volume":"186","author":"P Sharma","year":"2023","unstructured":"Sharma P, Goswami S, Raychaudhuri D, et al. Immune checkpoint therapy-current perspectives and future directions. Cell. 2023;186(8):1652\u201369.","journal-title":"Cell"},{"issue":"26","key":"837_CR2","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","volume":"366","author":"SL Topalian","year":"2012","unstructured":"Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366(26):2443\u201354.","journal-title":"N Engl J Med"},{"issue":"1","key":"837_CR3","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1186\/s13045-025-01734-x","volume":"18","author":"L Huang","year":"2025","unstructured":"Huang L, Zhu H, Shi Y. Immune checkpoint inhibitors for the treatment of solid tumors and lymphoma in the past 26 years (2000\u20132025). J Hematol Oncol. 2025;18(1):107.","journal-title":"J Hematol Oncol"},{"issue":"4","key":"837_CR4","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1016\/j.ccell.2020.03.017","volume":"37","author":"AJ Schoenfeld","year":"2020","unstructured":"Schoenfeld AJ, Hellmann MD. Acquired resistance to immune checkpoint inhibitors. Cancer Cell. 2020;37(4):443\u201355.","journal-title":"Cancer Cell"},{"issue":"1","key":"837_CR5","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1146\/annurev-immunol-101819-024752","volume":"42","author":"HN Bell","year":"2024","unstructured":"Bell HN, Zou W. Beyond the barrier: unraveling the mechanisms of immunotherapy resistance. Annu Rev Immunol. 2024;42(1):521\u201350.","journal-title":"Annu Rev Immunol"},{"issue":"5","key":"837_CR6","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","volume":"24","author":"M Binnewies","year":"2018","unstructured":"Binnewies M, Roberts EW, Kersten K, et al. Understanding the tumor immune microenvironment (TIME) for effective therapy. Nat Med. 2018;24(5):541\u201350.","journal-title":"Nat Med"},{"issue":"1","key":"837_CR7","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1186\/s40164-024-00543-1","volume":"13","author":"S Zheng","year":"2024","unstructured":"Zheng S, Wang W, Shen L, et al. Tumor battlefield within inflamed, excluded or desert immune phenotypes: the mechanisms and strategies. Exp Hematol Oncol. 2024;13(1):80.","journal-title":"Exp Hematol Oncol"},{"issue":"7637","key":"837_CR8","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(7637):321\u201330.","journal-title":"Nature"},{"issue":"1","key":"837_CR9","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s40164-025-00695-8","volume":"14","author":"M Radandish","year":"2025","unstructured":"Radandish M, Mashhadi N, Aghayan AH, et al. In-depth insight into tumor-infiltrating stromal cells linked to tertiary lymphoid structures and their prospective function in cancer immunotherapy. Exp Hematol Oncol. 2025;14(1):105.","journal-title":"Exp Hematol Oncol"},{"issue":"1","key":"837_CR10","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s40164-024-00532-4","volume":"13","author":"Y Zhang","year":"2024","unstructured":"Zhang Y, Wang C, Li JJ. Revisiting the role of mesenchymal stromal cells in cancer initiation, metastasis and immunosuppression. Exp Hematol Oncol. 2024;13(1):64.","journal-title":"Exp Hematol Oncol"},{"issue":"1","key":"837_CR11","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/s40164-025-00688-7","volume":"14","author":"L Sun","year":"2025","unstructured":"Sun L, Cao X, Zhou B, et al. Tumor-associated mesenchymal stem\/stromal cells in tumor microenvironment and carcinogenesis. Exp Hematol Oncol. 2025;14(1):97.","journal-title":"Exp Hematol Oncol"},{"issue":"9","key":"837_CR12","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1038\/nrc.2016.73","volume":"16","author":"R Kalluri","year":"2016","unstructured":"Kalluri R. The biology and function of fibroblasts in cancer. Nat Rev Cancer. 2016;16(9):582\u201398.","journal-title":"Nat Rev Cancer"},{"issue":"3","key":"837_CR13","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.ccell.2023.02.015","volume":"41","author":"G Caligiuri","year":"2023","unstructured":"Caligiuri G, Tuveson DA. Activated fibroblasts in cancer: perspectives and challenges. Cancer Cell. 2023;41(3):434\u201349.","journal-title":"Cancer Cell"},{"issue":"1","key":"837_CR14","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s40164-025-00647-2","volume":"14","author":"M Zhang","year":"2025","unstructured":"Zhang M, Zhang B. Extracellular matrix stiffness: mechanisms in tumor progression and therapeutic potential in cancer. Exp Hematol Oncol. 2025;14(1):54.","journal-title":"Exp Hematol Oncol"},{"issue":"3","key":"837_CR15","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.ccell.2018.01.011","volume":"33","author":"A Costa","year":"2018","unstructured":"Costa A, Kieffer Y, Scholer-Dahirel A, et al. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell. 2018;33(3):463\u201379.","journal-title":"Cancer Cell"},{"issue":"3","key":"837_CR16","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1038\/s41568-019-0238-1","volume":"20","author":"E Sahai","year":"2020","unstructured":"Sahai E, Astsaturov I, Cukierman E, et al. A framework for advancing our understanding of cancer-associated fibroblasts. Nat Rev Cancer. 2020;20(3):174\u201386.","journal-title":"Nat Rev Cancer"},{"issue":"7","key":"837_CR17","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/s43018-022-00411-z","volume":"3","author":"D Lavie","year":"2022","unstructured":"Lavie D, Ben-Shmuel A, Erez N, et al. Cancer-associated fibroblasts in the single-cell era. Nat Cancer. 2022;3(7):793\u2013807.","journal-title":"Nat Cancer"},{"issue":"7","key":"837_CR18","doi-asserted-by":"publisher","first-page":"1322","DOI":"10.1038\/s12276-023-01013-0","volume":"55","author":"D Yang","year":"2023","unstructured":"Yang D, Liu J, Qian H, et al. Cancer-associated fibroblasts: from basic science to anticancer therapy. Exp Mol Med. 2023;55(7):1322\u201332.","journal-title":"Exp Mol Med"},{"issue":"14","key":"837_CR19","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1038\/s41388-026-03733-9","volume":"45","author":"J Adams","year":"2026","unstructured":"Adams J, Suelzu CM, Strusi G, et al. Cancer-associated fibroblasts as key regulators of lipid metabolism in the tumour microenvironment. Oncogene. 2026;45(14):1211\u201319.","journal-title":"Oncogene"},{"issue":"5","key":"837_CR20","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/j.ccell.2024.03.005","volume":"42","author":"N Niu","year":"2024","unstructured":"Niu N, Shen X, Wang Z, et al. Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer. Cancer Cell. 2024;42(5):869\u201384.","journal-title":"Cancer Cell"},{"issue":"12","key":"837_CR21","doi-asserted-by":"publisher","first-page":"2008","DOI":"10.1038\/s41590-023-01675-y","volume":"24","author":"GR Bantug","year":"2023","unstructured":"Bantug GR, Hess C. The immunometabolic ecosystem in cancer. Nat Immunol. 2023;24(12):2008\u201320.","journal-title":"Nat Immunol"},{"issue":"8082","key":"837_CR22","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1038\/s41586-025-09303-5","volume":"645","author":"J Heide","year":"2025","unstructured":"Heide J, Bilecz AJ, Patnaik S, et al. NNMT inhibition in cancer-associated fibroblasts restores antitumour immunity. Nature. 2025;645(8082):1051\u201359.","journal-title":"Nature"},{"issue":"9","key":"837_CR23","doi-asserted-by":"publisher","first-page":"e20241426","DOI":"10.1084\/jem.20241426","volume":"222","author":"X Li","year":"2025","unstructured":"Li X, M\u00f8ller SH, Park J, et al. Tumor-instructed glutamine synthesis in cancer-associated fibroblasts promotes pro-tumor macrophages. J Exp Med. 2025;222(9):e20241426.","journal-title":"J Exp Med"},{"issue":"10","key":"837_CR24","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/s41568-024-00740-4","volume":"24","author":"L Arpinati","year":"2024","unstructured":"Arpinati L, Carradori G, Scherz-Shouval R. CAF-induced physical constraints controlling T cell state and localization in solid tumours. Nat Rev Cancer. 2024;24(10):676\u201393.","journal-title":"Nat Rev Cancer"},{"issue":"6","key":"837_CR25","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1038\/s41568-025-00798-8","volume":"25","author":"Z Xiao","year":"2025","unstructured":"Xiao Z, Pur\u00e9 E. The fibroinflammatory response in cancer. Nat Rev Cancer. 2025;25(6):399\u2013425.","journal-title":"Nat Rev Cancer"},{"issue":"2","key":"837_CR26","doi-asserted-by":"publisher","first-page":"366","DOI":"10.1038\/s12276-026-01650-1","volume":"58","author":"TH Kim","year":"2026","unstructured":"Kim TH, Lim SH, Lee H, et al. Metabolic crosstalk among cancer-associated fibroblasts, adipocytes and immune cells as an immunosuppressive tumor microenvironment driver. Exp Mol Med. 2026;58(2):366\u201381.","journal-title":"Exp Mol Med"},{"issue":"18","key":"837_CR27","doi-asserted-by":"publisher","first-page":"4668","DOI":"10.1158\/0008-5472.CAN-21-2553","volume":"81","author":"E Cukierman","year":"2021","unstructured":"Cukierman E. A reflection on how carcinoma-associated fibroblasts were recognized as active participants of epithelial tumorigenesis. Cancer Res. 2021;81(18):4668\u201370.","journal-title":"Cancer Res"},{"issue":"1","key":"837_CR28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-022-34464-6","volume":"14","author":"L Han","year":"2023","unstructured":"Han L, Wu Y, Fang K, et al. The splanchnic mesenchyme is the tissue of origin for pancreatic fibroblasts during homeostasis and tumorigenesis. Nat Commun. 2023;14(1):1.","journal-title":"Nat Commun"},{"issue":"5","key":"837_CR29","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.3390\/ijms19051294","volume":"19","author":"L Caja","year":"2018","unstructured":"Caja L, Dituri F, Mancarella S, et al. TGF-\u03b2 and the tissue microenvironment: relevance in fibrosis and cancer. Int J Mol Sci. 2018;19(5):1294.","journal-title":"Int J Mol Sci"},{"issue":"2","key":"837_CR30","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1158\/2159-8290.CD-18-0710","volume":"9","author":"G Biffi","year":"2019","unstructured":"Biffi G, Oni TE, Spielman B, et al. IL1-induced JAK\/STAT signaling is antagonized by TGF\u03b2 to shape CAF heterogeneity in pancreatic ductal adenocarcinoma. Cancer Discov. 2019;9(2):282\u2013301.","journal-title":"Cancer Discov"},{"issue":"2","key":"837_CR31","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41389-021-00302-5","volume":"10","author":"H Yoon","year":"2021","unstructured":"Yoon H, Tang C, Banerjee S, et al. TGF-\u03b21-mediated transition of resident fibroblasts to cancer-associated fibroblasts promotes cancer metastasis in gastrointestinal stromal tumor. Oncogenesis. 2021;10(2):13.","journal-title":"Oncogenesis"},{"issue":"6","key":"837_CR32","first-page":"3743","volume":"19","author":"M Lazarevic","year":"2020","unstructured":"Lazarevic M, Milosevic M, Jelovac D, et al. Marked epithelial to mesenchymal transition in surgical margins of oral cancer-an in vitro study. Oncol Lett. 2020;19(6):3743\u201350.","journal-title":"Oncol Lett"},{"issue":"7","key":"837_CR33","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1016\/j.cell.2017.10.044","volume":"171","author":"SV Puram","year":"2017","unstructured":"Puram SV, Tirosh I, Parikh AS, et al. Single-cell transcriptomic analysis of primary and metastatic tumor ecosystems in head and neck cancer. Cell. 2017;171(7):1611\u201324.","journal-title":"Cell"},{"issue":"21","key":"837_CR34","doi-asserted-by":"publisher","first-page":"10123","DOI":"10.1158\/0008-5472.CAN-07-3127","volume":"67","author":"EM Zeisberg","year":"2007","unstructured":"Zeisberg EM, Potenta S, Xie L, et al. Discovery of endothelial to mesenchymal transition as a source for carcinoma-associated fibroblasts. Cancer Res. 2007;67(21):10123\u20138.","journal-title":"Cancer Res"},{"issue":"5","key":"837_CR35","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1038\/s12276-020-0439-4","volume":"52","author":"KJ Choi","year":"2020","unstructured":"Choi KJ, Nam JK, Kim JH, et al. Endothelial-to-mesenchymal transition in anticancer therapy and normal tissue damage. Exp Mol Med. 2020;52(5):781\u201392.","journal-title":"Exp Mol Med"},{"issue":"23","key":"837_CR36","doi-asserted-by":"publisher","first-page":"8492","DOI":"10.1158\/0008-5472.CAN-04-1708","volume":"64","author":"NC Direkze","year":"2004","unstructured":"Direkze NC, Hodivala-Dilke K, Jeffery R, et al. Bone marrow contribution to tumor-associated myofibroblasts and fibroblasts. Cancer Res. 2004;64(23):8492\u20135.","journal-title":"Cancer Res"},{"issue":"2","key":"837_CR37","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.ccr.2011.01.020","volume":"19","author":"M Quante","year":"2011","unstructured":"Quante M, Tu SP, Tomita H, et al. Bone marrow-derived myofibroblasts contribute to the mesenchymal stem cell niche and promote tumor growth. Cancer Cell. 2011;19(2):257\u201372.","journal-title":"Cancer Cell"},{"issue":"38","key":"837_CR38","doi-asserted-by":"publisher","first-page":"E5618","DOI":"10.1073\/pnas.1608384113","volume":"113","author":"K Hosaka","year":"2016","unstructured":"Hosaka K, Yang Y, Seki T, et al. Pericyte-fibroblast transition promotes tumor growth and metastasis. Proc Natl Acad Sci U S A. 2016;113(38):E5618\u201327.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"837_CR39","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41467-023-35793-w","volume":"14","author":"JM Houthuijzen","year":"2023","unstructured":"Houthuijzen JM, de Bruijn R, van der Burg E, et al. CD26-negative and CD26-positive tissue-resident fibroblasts contribute to functionally distinct CAF subpopulations in breast cancer. Nat Commun. 2023;14(1):183.","journal-title":"Nat Commun"},{"issue":"3","key":"837_CR40","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/j.jcmgh.2020.05.004","volume":"10","author":"PE Garcia","year":"2020","unstructured":"Garcia PE, Adoumie M, Kim EC, et al. Differential contribution of pancreatic fibroblast subsets to the pancreatic cancer stroma. Cell Mol Gastroenterol Hepatol. 2020;10(3):581\u201399.","journal-title":"Cell Mol Gastroenterol Hepatol"},{"issue":"11","key":"837_CR41","doi-asserted-by":"publisher","first-page":"2606","DOI":"10.1158\/2159-8290.CD-21-1714","volume":"12","author":"JA Grout","year":"2022","unstructured":"Grout JA, Sirven P, Leader AM, et al. Spatial positioning and matrix programs of cancer-associated fibroblasts promote T-cell exclusion in human lung tumors. Cancer Discov. 2022;12(11):2606\u201325.","journal-title":"Cancer Discov"},{"issue":"5","key":"837_CR42","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/j.ccell.2025.03.004","volume":"43","author":"Y Liu","year":"2025","unstructured":"Liu Y, Sinjab A, Min J, et al. Conserved spatial subtypes and cellular neighborhoods of cancer-associated fibroblasts revealed by single-cell spatial multi-omics. Cancer Cell. 2025;43(5):905\u201324.","journal-title":"Cancer Cell"},{"issue":"1","key":"837_CR43","doi-asserted-by":"publisher","first-page":"6619","DOI":"10.1038\/s41467-022-34395-2","volume":"13","author":"H Luo","year":"2022","unstructured":"Luo H, Xia X, Huang LB, et al. Pan-cancer single-cell analysis reveals the heterogeneity and plasticity of cancer-associated fibroblasts in the tumor microenvironment. Nat Commun. 2022;13(1):6619.","journal-title":"Nat Commun"},{"issue":"1","key":"837_CR44","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s12943-023-01876-x","volume":"22","author":"C Ma","year":"2023","unstructured":"Ma C, Yang C, Peng A, et al. Pan-cancer spatially resolved single-cell analysis reveals the crosstalk between cancer-associated fibroblasts and tumor microenvironment. Mol Cancer. 2023;22(1):170.","journal-title":"Mol Cancer"},{"issue":"22","key":"837_CR45","doi-asserted-by":"publisher","first-page":"7020","DOI":"10.1158\/1078-0432.CCR-09-1126","volume":"15","author":"MA Troester","year":"2009","unstructured":"Troester MA, Lee MH, Carter M, et al. Activation of host wound responses in breast cancer microenvironment. Clin Cancer Res. 2009;15(22):7020\u20138.","journal-title":"Clin Cancer Res"},{"issue":"1","key":"837_CR46","doi-asserted-by":"publisher","first-page":"4692","DOI":"10.1038\/s41467-018-06654-8","volume":"9","author":"A Chakravarthy","year":"2018","unstructured":"Chakravarthy A, Khan L, Bensler NP, et al. TGF-\u03b2-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure. Nat Commun. 2018;9(1):4692.","journal-title":"Nat Commun"},{"issue":"15","key":"837_CR47","doi-asserted-by":"publisher","first-page":"3561","DOI":"10.1158\/1078-0432.CCR-14-1051","volume":"21","author":"CJ Whatcott","year":"2015","unstructured":"Whatcott CJ, Diep CH, Jiang P, et al. Desmoplasia in primary tumors and metastatic lesions of pancreatic cancer. Clin Cancer Res. 2015;21(15):3561\u20138.","journal-title":"Clin Cancer Res"},{"issue":"19","key":"837_CR48","doi-asserted-by":"publisher","first-page":"5995","DOI":"10.1158\/1078-0432.CCR-08-0291","volume":"14","author":"JM Bailey","year":"2008","unstructured":"Bailey JM, Swanson BJ, Hamada T, et al. Sonic hedgehog promotes desmoplasia in pancreatic cancer. Clin Cancer Res. 2008;14(19):5995\u20136004.","journal-title":"Clin Cancer Res"},{"issue":"11","key":"837_CR49","doi-asserted-by":"publisher","first-page":"4254","DOI":"10.1073\/pnas.0813203106","volume":"106","author":"H Tian","year":"2009","unstructured":"Tian H, Callahan CA, DuPree KJ, et al. Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis. Proc Natl Acad Sci U S A. 2009;106(11):4254\u201359.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"3","key":"837_CR50","doi-asserted-by":"publisher","first-page":"109009","DOI":"10.1016\/j.celrep.2021.109009","volume":"35","author":"N Bota-Rabassedas","year":"2021","unstructured":"Bota-Rabassedas N, Banerjee P, Niu Y, et al. Contextual cues from cancer cells govern cancer-associated fibroblast heterogeneity. Cell Rep. 2021;35(3):109009.","journal-title":"Cell Rep"},{"issue":"10","key":"837_CR51","doi-asserted-by":"publisher","first-page":"2536","DOI":"10.1002\/stem.2412","volume":"34","author":"P Barcellos-de-Souza","year":"2016","unstructured":"Barcellos-de-Souza P, Comito G, Pons-Segura C, et al. Mesenchymal stem cells are recruited and activated into carcinoma-associated fibroblasts by prostate cancer microenvironment-derived TGF-\u03b21. Stem Cells. 2016;34(10):2536\u201347.","journal-title":"Stem Cells"},{"issue":"17","key":"837_CR52","doi-asserted-by":"publisher","first-page":"2952","DOI":"10.1158\/0008-5472.CAN-22-3034","volume":"83","author":"G Davidson","year":"2023","unstructured":"Davidson G, Helleux A, Vano YA, et al. Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear cell renal cell carcinoma. Cancer Res. 2023;83(17):2952\u201369.","journal-title":"Cancer Res"},{"issue":"6","key":"837_CR53","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1038\/ncb2756","volume":"15","author":"F Calvo","year":"2013","unstructured":"Calvo F, Ege N, Grande-Garcia A, et al. Mechanotransduction and YAP-dependent matrix remodelling is required for the generation and maintenance of cancer-associated fibroblasts. Nat Cell Biol. 2013;15(6):637\u201346.","journal-title":"Nat Cell Biol"},{"issue":"1","key":"837_CR54","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1186\/s13046-019-1110-6","volume":"38","author":"NI Nissen","year":"2019","unstructured":"Nissen NI, Karsdal M, Willumsen N. Collagens and cancer associated fibroblasts in the reactive stroma and its relation to cancer biology. J Exp Clin Cancer Res. 2019;38(1):115.","journal-title":"J Exp Clin Cancer Res"},{"issue":"2","key":"837_CR55","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1158\/0008-5472.CAN-23-1448","volume":"84","author":"C Li","year":"2024","unstructured":"Li C, Guo H, Zhai P, et al. Spatial and single-cell transcriptomics reveal a cancer-associated fibroblast subset in HNSCC that restricts infiltration and antitumor activity of CD8+ T cells. Cancer Res. 2024;84(2):258\u201375.","journal-title":"Cancer Res"},{"issue":"2","key":"837_CR56","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.ccr.2009.12.041","volume":"17","author":"N Erez","year":"2010","unstructured":"Erez N, Truitt M, Olson P, et al. Cancer-associated fibroblasts are activated in incipient neoplasia to orchestrate tumor-promoting inflammation in an NF-\u03baB-dependent manner. Cancer Cell. 2010;17(2):135\u201347.","journal-title":"Cancer Cell"},{"issue":"1","key":"837_CR57","doi-asserted-by":"publisher","first-page":"4251","DOI":"10.1038\/s41467-023-39953-w","volume":"14","author":"E Koncina","year":"2023","unstructured":"Koncina E, Nurmik M, Pozdeev VI, et al. IL1R1+ cancer-associated fibroblasts drive tumor development and immunosuppression in colorectal cancer. Nat Commun. 2023;14(1):4251.","journal-title":"Nat Commun"},{"issue":"1","key":"837_CR58","doi-asserted-by":"publisher","first-page":"9678","DOI":"10.1038\/s41467-024-53908-9","volume":"15","author":"A Forsthuber","year":"2024","unstructured":"Forsthuber A, Aschenbrenner B, Korosec A, et al. Cancer-associated fibroblast subtypes modulate the tumor-immune microenvironment and are associated with skin cancer malignancy. Nat Commun. 2024;15(1):9678.","journal-title":"Nat Commun"},{"issue":"8","key":"837_CR59","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1158\/2159-8290.CD-19-0094","volume":"9","author":"E Elyada","year":"2019","unstructured":"Elyada E, Bolisetty M, Laise P, et al. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov. 2019;9(8):1102\u201323.","journal-title":"Cancer Discov"},{"issue":"6","key":"837_CR60","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, et al. Mesothelial cell-derived antigen-presenting cancer-associated fibroblasts induce expansion of regulatory T cells in pancreatic cancer. Cancer Cell. 2022;40(6):656\u201373.","journal-title":"Cancer Cell"},{"issue":"1","key":"837_CR61","doi-asserted-by":"publisher","first-page":"4988","DOI":"10.1038\/s41467-024-49282-1","volume":"15","author":"A Varveri","year":"2024","unstructured":"Varveri A, Papadopoulou M, Papadovasilakis Z, et al. Immunological synapse formation between T regulatory cells and cancer-associated fibroblasts promotes tumour development. Nat Commun. 2024;15(1):4988.","journal-title":"Nat Commun"},{"issue":"3","key":"837_CR62","doi-asserted-by":"publisher","first-page":"102017","DOI":"10.1016\/j.xcrm.2025.102017","volume":"6","author":"Z Cao","year":"2025","unstructured":"Cao Z, Meng Z, Li J, et al. Interferon-\u03b3-stimulated antigen-presenting cancer-associated fibroblasts hinder neoadjuvant chemoimmunotherapy efficacy in lung cancer. Cell Rep Med. 2025;6(3):102017.","journal-title":"Cell Rep Med"},{"issue":"7","key":"837_CR63","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1016\/j.ccell.2026.06.001","volume":"44","author":"Y Liu","year":"2026","unstructured":"Liu Y, Chen X, Dai Y, et al. Molecular phenotypes and spatial archetypes: a new framework for cancer-associated fibroblasts. Cancer Cell. 2026;44(7):1346\u201367.","journal-title":"Cancer Cell"},{"issue":"3","key":"837_CR64","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1084\/jem.20162024","volume":"214","author":"D \u00d6hlund","year":"2017","unstructured":"\u00d6hlund D, Handly-Santana A, Biffi G, et al. Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer. J Exp Med. 2017;214(3):579\u201396.","journal-title":"J Exp Med"},{"issue":"19","key":"837_CR65","doi-asserted-by":"publisher","first-page":"e104063","DOI":"10.15252\/embj.2019104063","volume":"39","author":"SZ Wu","year":"2020","unstructured":"Wu SZ, Roden DL, Wang C, et al. Stromal cell diversity associated with immune evasion in human triple-negative breast cancer. EMBO J. 2020;39(19):e104063.","journal-title":"EMBO J"},{"issue":"1","key":"837_CR66","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s12943-024-02191-9","volume":"24","author":"BH Jenkins","year":"2025","unstructured":"Jenkins BH, Tracy I, Rodrigues MFSD, et al. Single cell and spatial analysis of immune-hot and immune-cold tumours identifies fibroblast subtypes associated with distinct immunological niches and positive immunotherapy response. Mol Cancer. 2025;24(1):3.","journal-title":"Mol Cancer"},{"issue":"1","key":"837_CR67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41421-024-00747-z","volume":"11","author":"Y Cheng","year":"2025","unstructured":"Cheng Y, Chen X, Feng L, et al. Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma. Cell Discov. 2025;11(1):1.","journal-title":"Cell Discov"},{"issue":"1","key":"837_CR68","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1038\/s41467-025-57465-7","volume":"16","author":"J Song","year":"2025","unstructured":"Song J, Wei R, Liu C, et al. Antigen-presenting cancer associated fibroblasts enhance antitumor immunity and predict immunotherapy response. Nat Commun. 2025;16(1):2175.","journal-title":"Nat Commun"},{"issue":"10","key":"837_CR69","doi-asserted-by":"publisher","first-page":"e1438","DOI":"10.1002\/ctm2.1438","volume":"13","author":"JI Choi","year":"2023","unstructured":"Choi JI, Cho EJ, Yang MJ, et al. Hypoxic microenvironment determines the phenotypic plasticity and spatial distribution of cancer-associated fibroblasts. Clin Transl Med. 2023;13(10):e1438.","journal-title":"Clin Transl Med"},{"issue":"10","key":"837_CR70","doi-asserted-by":"publisher","first-page":"1596","DOI":"10.1158\/0008-5472.CAN-22-2316","volume":"83","author":"S Schw\u00f6rer","year":"2023","unstructured":"Schw\u00f6rer S, Cimino FV, Ros M, et al. Hypoxia potentiates the inflammatory fibroblast phenotype promoted by pancreatic cancer cell-derived cytokines. Cancer Res. 2023;83(10):1596\u2013610.","journal-title":"Cancer Res"},{"issue":"9","key":"837_CR71","doi-asserted-by":"publisher","first-page":"1677","DOI":"10.1016\/j.ccell.2025.06.021","volume":"43","author":"Y Zhang","year":"2025","unstructured":"Zhang Y, Ling L, Murad R, et al. Macropinocytosis maintains CAF subtype identity under metabolic stress in pancreatic cancer. Cancer Cell. 2025;43(9):1677\u201396.","journal-title":"Cancer Cell"},{"issue":"6","key":"837_CR72","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s42255-022-00582-0","volume":"4","author":"EJ Kay","year":"2022","unstructured":"Kay EJ, Paterson K, Riera-Domingo C, et al. Cancer-associated fibroblasts require proline synthesis by PYCR1 for the deposition of pro-tumorigenic extracellular matrix. Nat Metab. 2022;4(6):693\u2013710.","journal-title":"Nat Metab"},{"issue":"1","key":"837_CR73","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1186\/s12943-024-02180-y","volume":"23","author":"X Zhou","year":"2024","unstructured":"Zhou X, Han J, Zuo A, et al. THBS2+ cancer-associated fibroblasts promote EMT leading to oxaliplatin resistance via COL8A1-mediated PI3K\/AKT activation in colorectal cancer. Mol Cancer. 2024;23(1):282.","journal-title":"Mol Cancer"},{"issue":"1","key":"837_CR74","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s40164-025-00713-9","volume":"14","author":"SMA Salam","year":"2025","unstructured":"Salam SMA, Jahan E, Ahn EJ, et al. Brain metastasis-associated cancer fibroblasts drive tumor progression and therapeutic resistance through IL26 and CX3CL1 signaling in non-small-cell lung cancer. Exp Hematol Oncol. 2025;14(1):120.","journal-title":"Exp Hematol Oncol"},{"issue":"7934","key":"837_CR75","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/s41586-022-05272-1","volume":"611","author":"AT Krishnamurty","year":"2022","unstructured":"Krishnamurty AT, Shyer JA, Thai M, et al. LRRC15+ myofibroblasts dictate the stromal setpoint to suppress tumour immunity. Nature. 2022;611(7934):148\u201354.","journal-title":"Nature"},{"issue":"6","key":"837_CR76","doi-asserted-by":"publisher","first-page":"1580","DOI":"10.1158\/2159-8290.CD-20-1484","volume":"12","author":"KM McAndrews","year":"2022","unstructured":"McAndrews KM, Chen Y, Darpolor JK, et al. Identification of functional heterogeneity of carcinoma-associated fibroblasts with distinct IL6-mediated therapy resistance in pancreatic cancer. Cancer Discov. 2022;12(6):1580\u201397.","journal-title":"Cancer Discov"},{"issue":"4","key":"837_CR77","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.ccell.2021.02.007","volume":"39","author":"Y Chen","year":"2021","unstructured":"Chen Y, Kim J, Yang S, et al. Type I collagen deletion in \u03b1SMA+ myofibroblasts augments immune suppression and accelerates progression of pancreatic cancer. Cancer Cell. 2021;39(4):548\u201365.","journal-title":"Cancer Cell"},{"issue":"9","key":"837_CR78","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1016\/j.ccell.2021.06.017","volume":"39","author":"C Hutton","year":"2021","unstructured":"Hutton C, Heider F, Blanco-Gomez A, et al. Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity. Cancer Cell. 2021;39(9):1227\u201344.","journal-title":"Cancer Cell"},{"issue":"1","key":"837_CR79","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s40164-024-00533-3","volume":"13","author":"Z He","year":"2024","unstructured":"He Z, Li X, Chen S, et al. CD105+CAF-derived exosomes CircAMPK1 promotes pancreatic cancer progression by activating autophagy. Exp Hematol Oncol. 2024;13(1):79.","journal-title":"Exp Hematol Oncol"},{"issue":"22","key":"837_CR80","doi-asserted-by":"publisher","first-page":"3728","DOI":"10.1158\/0008-5472.CAN-24-0932","volume":"84","author":"H Song","year":"2024","unstructured":"Song H, Lu T, Han D, et al. YAP1 inhibition induces phenotype switching of cancer-associated fibroblasts to tumor suppressive in prostate cancer. Cancer Res. 2024;84(22):3728\u201342.","journal-title":"Cancer Res"},{"issue":"8","key":"837_CR81","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1016\/j.celrep.2015.02.006","volume":"10","author":"D Zhang","year":"2015","unstructured":"Zhang D, Wang Y, Shi Z, et al. Metabolic reprogramming of cancer-associated fibroblasts by IDH3\u03b1 downregulation. Cell Rep. 2015;10(8):1335\u201348.","journal-title":"Cell Rep"},{"issue":"5","key":"837_CR82","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/s41556-018-0083-6","volume":"20","author":"W Yan","year":"2018","unstructured":"Yan W, Wu X, Zhou W, et al. Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells. Nat Cell Biol. 2018;20(5):597\u2013609.","journal-title":"Nat Cell Biol"},{"issue":"3","key":"837_CR83","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1038\/s41388-019-1014-0","volume":"39","author":"JS Sung","year":"2020","unstructured":"Sung JS, Kang CW, Kang S, et al. ITGB4-mediated metabolic reprogramming of cancer-associated fibroblasts. Oncogene. 2020;39(3):664\u201376.","journal-title":"Oncogene"},{"issue":"23","key":"837_CR84","doi-asserted-by":"publisher","first-page":"3984","DOI":"10.4161\/cc.8.23.10238","volume":"8","author":"S Pavlides","year":"2009","unstructured":"Pavlides S, Whitaker-Menezes D, Castello-Cros R, et al. The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma. Cell Cycle. 2009;8(23):3984\u20134001.","journal-title":"Cell Cycle"},{"issue":"1","key":"837_CR85","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s40164-024-00482-x","volume":"13","author":"J Yang","year":"2024","unstructured":"Yang J, Shay C, Saba NF, et al. Cancer metabolism and carcinogenesis. Exp Hematol Oncol. 2024;13(1):10.","journal-title":"Exp Hematol Oncol"},{"issue":"11","key":"837_CR86","doi-asserted-by":"publisher","first-page":"1772","DOI":"10.4161\/cc.10.11.15659","volume":"10","author":"D Whitaker-Menezes","year":"2011","unstructured":"Whitaker-Menezes D, Martinez-Outschoorn UE, Lin Z, et al. Evidence for a stromal-epithelial lactate shuttle in human tumors: MCT4 is a marker of oxidative stress in cancer-associated fibroblasts. Cell Cycle. 2011;10(11):1772\u201383.","journal-title":"Cell Cycle"},{"issue":"11","key":"837_CR87","doi-asserted-by":"publisher","first-page":"1264","DOI":"10.1089\/ars.2011.4243","volume":"16","author":"S Pavlides","year":"2012","unstructured":"Pavlides S, Vera I, Gandara R, et al. Warburg meets autophagy: cancer-associated fibroblasts accelerate tumor growth and metastasis via oxidative stress, mitophagy, and aerobic glycolysis. Antioxid Redox Signal. 2012;16(11):1264\u201384.","journal-title":"Antioxid Redox Signal"},{"key":"837_CR88","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.ebiom.2019.02.025","volume":"41","author":"K Sun","year":"2019","unstructured":"Sun K, Tang S, Hou Y, et al. Oxidized ATM-mediated glycolysis enhancement in breast cancer-associated fibroblasts contributes to tumor invasion through lactate as metabolic coupling. EBioMedicine. 2019;41:370\u201383.","journal-title":"EBioMedicine"},{"issue":"20","key":"837_CR89","doi-asserted-by":"publisher","first-page":"e163022","DOI":"10.1172\/jci.insight.163022","volume":"8","author":"F Kitamura","year":"2023","unstructured":"Kitamura F, Semba T, Yasuda-Yoshihara N, et al. Cancer-associated fibroblasts reuse cancer-derived lactate to maintain a fibrotic and immunosuppressive microenvironment in pancreatic cancer. JCI Insight. 2023;8(20):e163022.","journal-title":"JCI Insight"},{"issue":"5","key":"837_CR90","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1016\/j.cmet.2016.10.011","volume":"24","author":"L Yang","year":"2016","unstructured":"Yang L, Achreja A, Yeung TL, et al. Targeting stromal glutamine synthetase in tumors disrupts tumor microenvironment-regulated cancer cell growth. Cell Metab. 2016;24(5):685\u2013700.","journal-title":"Cell Metab"},{"key":"837_CR91","doi-asserted-by":"publisher","first-page":"e50663","DOI":"10.7554\/eLife.50663","volume":"8","author":"TD Bhagat","year":"2019","unstructured":"Bhagat TD, Von Ahrens D, Dawlaty M, et al. Lactate-mediated epigenetic reprogramming regulates formation of human pancreatic cancer-associated fibroblasts. Elife. 2019;8:e50663.","journal-title":"Elife"},{"issue":"9","key":"837_CR92","doi-asserted-by":"publisher","first-page":"107701","DOI":"10.1016\/j.celrep.2020.107701","volume":"31","author":"LM Becker","year":"2020","unstructured":"Becker LM, O\u2019Connell JT, Vo AP, et al. Epigenetic reprogramming of cancer-associated fibroblasts deregulates glucose metabolism and facilitates progression of breast cancer. Cell Rep. 2020;31(9):107701.","journal-title":"Cell Rep"},{"issue":"7758","key":"837_CR93","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1038\/s41586-019-1173-8","volume":"569","author":"MA Eckert","year":"2019","unstructured":"Eckert MA, Coscia F, Chryplewicz A, et al. Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts. Nature. 2019;569(7758):723\u201328.","journal-title":"Nature"},{"issue":"16","key":"837_CR94","doi-asserted-by":"publisher","first-page":"4098","DOI":"10.1158\/0008-5472.CAN-25-5716","volume":"86","author":"S Zhang","year":"2026","unstructured":"Zhang S, Yuan H, Guo M, et al. Mitophagy-competent cancer-associated fibroblasts fuel chemoresistance by rewiring pyrimidine metabolism in pancreatic cancer. Cancer Res. 2026;86(16):4098\u2013114.","journal-title":"Cancer Res"},{"issue":"1","key":"837_CR95","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1186\/s40164-025-00689-6","volume":"14","author":"R Wang","year":"2025","unstructured":"Wang R, Zhuang J, Zhang Q, et al. Decoding the metabolic dialogue in the tumor microenvironment: from immune suppression to precision cancer therapies. Exp Hematol Oncol. 2025;14(1):99.","journal-title":"Exp Hematol Oncol"},{"issue":"1","key":"837_CR96","doi-asserted-by":"publisher","first-page":"2498","DOI":"10.1038\/s41467-024-46504-4","volume":"15","author":"MT Broz","year":"2024","unstructured":"Broz MT, Ko EY, Ishaya K, et al. Metabolic targeting of cancer associated fibroblasts overcomes T-cell exclusion and chemoresistance in soft-tissue sarcomas. Nat Commun. 2024;15(1):2498.","journal-title":"Nat Commun"},{"issue":"1","key":"837_CR97","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/s41419-025-07974-6","volume":"16","author":"Q Wang","year":"2025","unstructured":"Wang Q, Sun Y, Li J, et al. Targeting LINC01711 in FAP+ cancer-associated fibroblasts overcomes lactate-mediated immunosuppression and enhances anti-PD-1 efficacy in lung adenocarcinoma. Cell Death Dis. 2025;16(1):642.","journal-title":"Cell Death Dis"},{"issue":"19","key":"837_CR98","doi-asserted-by":"publisher","first-page":"e157649","DOI":"10.1172\/JCI157649","volume":"132","author":"S Hu","year":"2022","unstructured":"Hu S, Lu H, Xie W, et al. TDO2+ myofibroblasts mediate immune suppression in malignant transformation of squamous cell carcinoma. J Clin Invest. 2022;132(19):e157649.","journal-title":"J Clin Invest"},{"issue":"1","key":"837_CR99","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1038\/s41467-019-14060-x","volume":"11","author":"M Yu","year":"2020","unstructured":"Yu M, Guo G, Huang L, et al. CD73 on cancer-associated fibroblasts enhanced by the A2B-mediated feedforward circuit enforces an immune checkpoint. Nat Commun. 2020;11(1):515.","journal-title":"Nat Commun"},{"issue":"2","key":"837_CR100","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1007\/s00018-020-03517-8","volume":"78","author":"B \u00c9rsek","year":"2021","unstructured":"\u00c9rsek B, Sill\u00f3 P, Cakir U, et al. Melanoma-associated fibroblasts impair CD8+ T cell function and modify expression of immune checkpoint regulators via increased arginase activity. Cell Mol Life Sci. 2021;78(2):661\u201373.","journal-title":"Cell Mol Life Sci"},{"key":"837_CR101","doi-asserted-by":"publisher","first-page":"216095","DOI":"10.1016\/j.canlet.2023.216095","volume":"558","author":"W Ge","year":"2023","unstructured":"Ge W, Yue M, Lin R, et al. PLA2G2A+ cancer-associated fibroblasts mediate pancreatic cancer immune escape via impeding antitumor immune response of CD8+ cytotoxic T cells. Cancer Lett. 2023;558:216095.","journal-title":"Cancer Lett"},{"issue":"37","key":"837_CR102","doi-asserted-by":"publisher","first-page":"e21418","DOI":"10.1002\/advs.202521418","volume":"13","author":"S Lu","year":"2026","unstructured":"Lu S, Ke S, Yu H, et al. Cancer-associated fibroblasts promote tumor immunosuppression in hepatocellular carcinoma via the NNMT-ANGPTL4 axis. Adv Sci (Weinh). 2026;13(37):e21418.","journal-title":"Adv Sci (Weinh)"},{"issue":"2","key":"837_CR103","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1158\/2159-8290.CD-20-0775","volume":"11","author":"R Francescone","year":"2021","unstructured":"Francescone R, Barbosa Vendramini-Costa D, Franco-Barraza J, et al. Netrin G1 promotes pancreatic tumorigenesis through cancer-associated fibroblast-driven nutritional support and immunosuppression. Cancer Discov. 2021;11(2):446\u201379.","journal-title":"Cancer Discov"},{"issue":"8","key":"837_CR104","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1158\/0008-5472.CAN-21-2778","volume":"82","author":"R Wei","year":"2022","unstructured":"Wei R, Zhou Y, Li C, et al. Ketogenesis attenuates KLF5-dependent production of CXCL12 to overcome the immunosuppressive tumor microenvironment in colorectal cancer. Cancer Res. 2022;82(8):1575\u201388.","journal-title":"Cancer Res"},{"issue":"2","key":"837_CR105","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.canlet.2011.12.020","volume":"318","author":"T Li","year":"2012","unstructured":"Li T, Yang Y, Hua X, et al. Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO. Cancer Lett. 2012;318(2):154\u201361.","journal-title":"Cancer Lett"},{"key":"837_CR106","doi-asserted-by":"publisher","first-page":"100947","DOI":"10.1016\/j.drup.2023.100947","volume":"68","author":"R Du","year":"2023","unstructured":"Du R, Zhang X, Lu X, et al. PDPN positive CAFs contribute to HER2 positive breast cancer resistance to trastuzumab by inhibiting antibody-dependent NK cell-mediated cytotoxicity. Drug Resist Updat. 2023;68:100947.","journal-title":"Drug Resist Updat"},{"key":"837_CR107","doi-asserted-by":"publisher","first-page":"102923","DOI":"10.1016\/j.redox.2023.102923","volume":"67","author":"L Yao","year":"2023","unstructured":"Yao L, Hou J, Wu X, et al. Cancer-associated fibroblasts impair the cytotoxic function of NK cells in gastric cancer by inducing ferroptosis via iron regulation. Redox Biol. 2023;67:102923.","journal-title":"Redox Biol"},{"issue":"19","key":"837_CR108","doi-asserted-by":"publisher","first-page":"3681","DOI":"10.1038\/s41388-019-0688-7","volume":"38","author":"G Comito","year":"2019","unstructured":"Comito G, Iscaro A, Bacci M, et al. Lactate modulates CD4+ T-cell polarization and induces an immunosuppressive environment, which sustains prostate carcinoma progression via TLR8\/miR21 axis. Oncogene. 2019;38(19):3681\u201395.","journal-title":"Oncogene"},{"issue":"9","key":"837_CR109","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/s41423-023-01061-6","volume":"20","author":"M Bied","year":"2023","unstructured":"Bied M, Ho WW, Ginhoux F, et al. Roles of macrophages in tumor development: a spatiotemporal perspective. Cell Mol Immunol. 2023;20(9):983\u201392.","journal-title":"Cell Mol Immunol"},{"issue":"10","key":"837_CR110","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1038\/ni.1937","volume":"11","author":"SK Biswas","year":"2010","unstructured":"Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11(10):889\u201396.","journal-title":"Nat Immunol"},{"issue":"1","key":"837_CR111","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s40164-024-00550-2","volume":"13","author":"W Chen","year":"2024","unstructured":"Chen W, Chen M, Hong L, et al. M2-like tumor-associated macrophage-secreted CCL2 facilitates gallbladder cancer stemness and metastasis. Exp Hematol Oncol. 2024;13(1):83.","journal-title":"Exp Hematol Oncol"},{"issue":"12","key":"837_CR112","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.it.2023.10.007","volume":"44","author":"I Nasir","year":"2023","unstructured":"Nasir I, McGuinness C, Poh AR, et al. Tumor macrophage functional heterogeneity can inform the development of novel cancer therapies. Trends Immunol. 2023;44(12):971\u201385.","journal-title":"Trends Immunol"},{"issue":"1","key":"837_CR113","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40164-023-00469-0","volume":"13","author":"M Cao","year":"2024","unstructured":"Cao M, Wang Z, Lan W, et al. The roles of tissue resident macrophages in health and cancer. Exp Hematol Oncol. 2024;13(1):3.","journal-title":"Exp Hematol Oncol"},{"issue":"1","key":"837_CR114","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1186\/s12943-024-02064-1","volume":"23","author":"X Chu","year":"2024","unstructured":"Chu X, Tian Y, Lv C. Decoding the spatiotemporal heterogeneity of tumor-associated macrophages. Mol Cancer. 2024;23(1):150.","journal-title":"Mol Cancer"},{"issue":"18","key":"837_CR115","doi-asserted-by":"publisher","first-page":"3291","DOI":"10.1158\/0008-5472.CAN-22-1427","volume":"82","author":"E Timperi","year":"2022","unstructured":"Timperi E, Gueguen P, Molgora M, et al. Lipid-associated macrophages are induced by cancer-associated fibroblasts and mediate immune suppression in breast cancer. Cancer Res. 2022;82(18):3291\u2013306.","journal-title":"Cancer Res"},{"issue":"2","key":"837_CR116","doi-asserted-by":"publisher","first-page":"e20210564","DOI":"10.1084\/jem.20210564","volume":"219","author":"M Masetti","year":"2022","unstructured":"Masetti M, Carriero R, Portale F, et al. Lipid-loaded tumor-associated macrophages sustain tumor growth and invasiveness in prostate cancer. J Exp Med. 2022;219(2):e20210564.","journal-title":"J Exp Med"},{"issue":"1","key":"837_CR117","doi-asserted-by":"publisher","first-page":"5665","DOI":"10.1038\/s41467-024-49885-8","volume":"15","author":"A Coulton","year":"2024","unstructured":"Coulton A, Murai J, Qian D, et al. Using a pan-cancer atlas to investigate tumour associated macrophages as regulators of immunotherapy response. Nat Commun. 2024;15(1):5665.","journal-title":"Nat Commun"},{"issue":"1","key":"837_CR118","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1186\/s40164-024-00587-3","volume":"13","author":"K Chen","year":"2024","unstructured":"Chen K, Li Y, Ni J, et al. Identification of a novel subtype of SPP1+ macrophages expressing SIRP\u03b1: implications for tumor immune evasion and treatment response prediction. Exp Hematol Oncol. 2024;13(1):119.","journal-title":"Exp Hematol Oncol"},{"key":"837_CR119","doi-asserted-by":"publisher","first-page":"103209","DOI":"10.1016\/j.redox.2024.103209","volume":"74","author":"X Gu","year":"2024","unstructured":"Gu X, Zhu Y, Su J, et al. Lactate-induced activation of tumor-associated fibroblasts and IL-8-mediated macrophage recruitment promote lung cancer progression. Redox Biol. 2024;74:103209.","journal-title":"Redox Biol"},{"issue":"8","key":"837_CR120","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1016\/j.cmet.2024.05.013","volume":"36","author":"Y Jiang","year":"2024","unstructured":"Jiang Y, Wang Y, Chen G, et al. Nicotinamide metabolism face-off between macrophages and fibroblasts manipulates the microenvironment in gastric cancer. Cell Metab. 2024;36(8):1806\u201322.","journal-title":"Cell Metab"},{"issue":"7","key":"837_CR121","doi-asserted-by":"publisher","first-page":"e009281","DOI":"10.1136\/jitc-2024-009281","volume":"12","author":"M Yang","year":"2024","unstructured":"Yang M, Wang B, Hou W, et al. NAD+ metabolism enzyme NNMT in cancer-associated fibroblasts drives tumor progression and resistance to immunotherapy by modulating macrophages in urothelial bladder cancer. J Immunother Cancer. 2024;12(7):e009281.","journal-title":"J Immunother Cancer"},{"issue":"1","key":"837_CR122","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s40164-024-00505-7","volume":"13","author":"J Lu","year":"2024","unstructured":"Lu J, Luo Y, Rao D, et al. Myeloid-derived suppressor cells in cancer: therapeutic targets to overcome tumor immune evasion. Exp Hematol Oncol. 2024;13(1):39.","journal-title":"Exp Hematol Oncol"},{"issue":"1","key":"837_CR123","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1186\/s12943-022-01657-y","volume":"21","author":"Y Wu","year":"2022","unstructured":"Wu Y, Yi M, Niu M, et al. Myeloid-derived suppressor cells: an emerging target for anticancer immunotherapy. Mol Cancer. 2022;21(1):184.","journal-title":"Mol Cancer"},{"issue":"1","key":"837_CR124","doi-asserted-by":"publisher","first-page":"9050","DOI":"10.1038\/s41467-024-53233-1","volume":"15","author":"K Zhang","year":"2024","unstructured":"Zhang K, Liu K, Hu B, et al. Iron-loaded cancer-associated fibroblasts induce immunosuppression in prostate cancer. Nat Commun. 2024;15(1):9050.","journal-title":"Nat Commun"},{"key":"837_CR125","doi-asserted-by":"publisher","first-page":"218243","DOI":"10.1016\/j.canlet.2026.218243","volume":"639","author":"Y Zhang","year":"2026","unstructured":"Zhang Y, Zhao H, Xu P, et al. The Zeb1\/system Xc\u2013 axis safeguards iron-loaded cancer-associated fibroblasts against ferroptosis and promotes immunosuppression in prostate cancer. Cancer Lett. 2026;639:218243.","journal-title":"Cancer Lett"},{"issue":"3","key":"837_CR126","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1038\/nri3399","volume":"13","author":"E Kolaczkowska","year":"2013","unstructured":"Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13(3):159\u201375.","journal-title":"Nat Rev Immunol"},{"issue":"3","key":"837_CR127","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.ccr.2009.06.017","volume":"16","author":"ZG Fridlender","year":"2009","unstructured":"Fridlender ZG, Sun J, Kim S, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: N1 versus N2 TAN. Cancer Cell. 2009;16(3):183\u201394.","journal-title":"Cancer Cell"},{"issue":"1","key":"837_CR128","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1186\/s13045-025-01731-0","volume":"18","author":"Y Feng","year":"2025","unstructured":"Feng Y, Liu G, Li H, et al. Target neutrophil heterogeneity and plasticity in cancer. J Hematol Oncol. 2025;18(1):79.","journal-title":"J Hematol Oncol"},{"issue":"3","key":"837_CR129","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1007\/s00262-025-03946-z","volume":"74","author":"T Yagi","year":"2025","unstructured":"Yagi T, Kagawa S, Nogi S, et al. Cancer-associated fibroblasts promote pro-tumor functions of neutrophils in pancreatic cancer via IL-8: potential suppression by pirfenidone. Cancer Immunol Immunother. 2025;74(3):96.","journal-title":"Cancer Immunol Immunother"},{"key":"837_CR130","first-page":"0901","volume":"8","author":"Z Zhao","year":"2025","unstructured":"Zhao Z, Cai H, Zhao Z, et al. Cancer-associated fibroblast-derived GDF15 induces oxidative stress and neutrophil infiltration in head and neck squamous cell carcinoma through the PI3K\/AKT\/STAT3 axis cascade. Res (Wash D C). 2025;8:0901.","journal-title":"Res (Wash D C)"},{"issue":"1","key":"837_CR131","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/s41467-021-20982-2","volume":"12","author":"H Munir","year":"2021","unstructured":"Munir H, Jones JO, Janowitz T, et al. Stromal-driven and amyloid \u03b2-dependent induction of neutrophil extracellular traps modulates tumor growth. Nat Commun. 2021;12(1):683.","journal-title":"Nat Commun"},{"key":"837_CR132","doi-asserted-by":"publisher","first-page":"175883592513875","DOI":"10.1177\/17588359251387551","volume":"17","author":"J Lv","year":"2025","unstructured":"Lv J, Chen X, Zhang R, et al. Neutrophil extracellular traps predict poor response and prognosis in non-small cell lung cancer immunotherapy. Ther Adv Med Oncol. 2025;17:17588359251387551.","journal-title":"Ther Adv Med Oncol"},{"issue":"8","key":"837_CR133","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1016\/j.ccell.2025.05.017","volume":"43","author":"F Huang","year":"2025","unstructured":"Huang F, Liu Z, Song Y, et al. Bile acids activate cancer-associated fibroblasts and induce an immunosuppressive microenvironment in cholangiocarcinoma. Cancer Cell. 2025;43(8):1460\u201375.","journal-title":"Cancer Cell"},{"issue":"4","key":"837_CR134","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1038\/s41419-018-0458-4","volume":"9","author":"Y Cheng","year":"2018","unstructured":"Cheng Y, Li H, Deng Y, et al. Cancer-associated fibroblasts induce PD-L1+ neutrophils through the IL6-STAT3 pathway that foster immune suppression in hepatocellular carcinoma. Cell Death Dis. 2018;9(4):422.","journal-title":"Cell Death Dis"},{"issue":"1","key":"837_CR135","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s40164-024-00571-x","volume":"13","author":"SZ Xie","year":"2024","unstructured":"Xie SZ, Yang LY, Wei R, et al. Targeting SPP1-orchestrated neutrophil extracellular traps-dominant pre-metastatic niche reduced HCC lung metastasis. Exp Hematol Oncol. 2024;13(1):111.","journal-title":"Exp Hematol Oncol"},{"key":"837_CR136","doi-asserted-by":"publisher","first-page":"101848","DOI":"10.1016\/j.smim.2023.101848","volume":"71","author":"C Moussion","year":"2024","unstructured":"Moussion C, Delamarre L. Antigen cross-presentation by dendritic cells: a critical axis in cancer immunotherapy. Semin Immunol. 2024;71:101848.","journal-title":"Semin Immunol"},{"key":"837_CR137","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1146\/annurev.immunol.20.100301.064828","volume":"20","author":"P Guermonprez","year":"2002","unstructured":"Guermonprez P, Valladeau J, Zitvogel L, et al. Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol. 2002;20:621\u201367.","journal-title":"Annu Rev Immunol"},{"issue":"7822","key":"837_CR138","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1038\/s41586-020-2611-3","volume":"584","author":"ST Ferris","year":"2020","unstructured":"Ferris ST, Durai V, Wu R, et al. cDC1 prime and are licensed by CD4+ T cells to induce anti-tumour immunity. Nature. 2020;584(7822):624\u201329.","journal-title":"Nature"},{"issue":"1","key":"837_CR139","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/s41419-025-08180-0","volume":"16","author":"Z Xie","year":"2025","unstructured":"Xie Z, Fang Y, Zhang X, et al. The emerging role of dendritic cells in the tumor microenvironment: from antigen presentation to targeted immunotherapy. Cell Death Dis. 2025;16(1):900.","journal-title":"Cell Death Dis"},{"issue":"2","key":"837_CR140","doi-asserted-by":"publisher","first-page":"e198","DOI":"10.1038\/oncsis.2016.7","volume":"5","author":"JT Cheng","year":"2016","unstructured":"Cheng JT, Deng YN, Yi HM, et al. Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation. Oncogenesis. 2016;5(2):e198.","journal-title":"Oncogenesis"},{"issue":"2","key":"837_CR141","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1136\/gutjnl-2020-322924","volume":"71","author":"TX Huang","year":"2022","unstructured":"Huang TX, Tan XY, Huang HS, et al. Targeting cancer-associated fibroblast-secreted WNT2 restores dendritic cell-mediated antitumour immunity. Gut. 2022;71(2):333\u201344.","journal-title":"Gut"},{"issue":"11","key":"837_CR142","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s00262-024-03809-z","volume":"73","author":"T Muijlwijk","year":"2024","unstructured":"Muijlwijk T, Wondergem NE, Ekhlas F, et al. Secretome and immune cell attraction analysis of head and neck cancers. Cancer Immunol Immunother. 2024;73(11):229.","journal-title":"Cancer Immunol Immunother"},{"issue":"7791","key":"837_CR143","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/s41586-019-1922-8","volume":"577","author":"BA Helmink","year":"2020","unstructured":"Helmink BA, Reddy SM, Gao J, et al. B cells and tertiary lymphoid structures promote immunotherapy response. Nature. 2020;577(7791):549\u201355.","journal-title":"Nature"},{"issue":"10","key":"837_CR144","doi-asserted-by":"publisher","first-page":"3505","DOI":"10.1158\/0008-5472.CAN-10-4316","volume":"71","author":"PB Olkhanud","year":"2011","unstructured":"Olkhanud PB, Damdinsuren B, Bodogai M, et al. Tumor-evoked regulatory B cells promote breast cancer metastasis by converting resting CD4\u207a T cells to T-regulatory cells. Cancer Res. 2011;71(10):3505\u201315.","journal-title":"Cancer Res"},{"issue":"1","key":"837_CR145","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s12935-025-03635-y","volume":"25","author":"X Fan","year":"2025","unstructured":"Fan X, Feng D, Wei D, et al. Characterizing tertiary lymphoid structures associated single-cell atlas in breast cancer patients. Cancer Cell Int. 2025;25(1):12.","journal-title":"Cancer Cell Int"},{"issue":"1","key":"837_CR146","doi-asserted-by":"publisher","first-page":"7713","DOI":"10.1038\/s41467-024-52153-4","volume":"15","author":"Y Liu","year":"2024","unstructured":"Liu Y, Ye SY, He S, et al. Single-cell and spatial transcriptome analyses reveal tertiary lymphoid structures linked to tumour progression and immunotherapy response in nasopharyngeal carcinoma. Nat Commun. 2024;15(1):7713.","journal-title":"Nat Commun"},{"issue":"4","key":"837_CR147","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s00262-026-04348-5","volume":"75","author":"X Li","year":"2026","unstructured":"Li X, Chen D, Guo Y, et al. Association of CCL21+ CAFs with B-cell recruitment and TLS maturation in penile squamous cell carcinoma. Cancer Immunol Immunother. 2026;75(4):109.","journal-title":"Cancer Immunol Immunother"},{"issue":"7","key":"837_CR148","doi-asserted-by":"publisher","first-page":"3228","DOI":"10.1158\/0008-5472.CAN-08-3000","volume":"69","author":"H Maby-El Hajjami","year":"2009","unstructured":"Maby-El Hajjami H, Am\u00e9-Thomas P, Pangault C, et al. Functional alteration of the lymphoma stromal cell niche by the cytokine context: role of indoleamine-2,3 dioxygenase. Cancer Res. 2009;69(7):3228\u201337.","journal-title":"Cancer Res"},{"issue":"5","key":"837_CR149","first-page":"1639","volume":"9","author":"AM Scott","year":"2003","unstructured":"Scott AM, Wiseman G, Welt S, et al. A phase I dose-escalation study of sibrotuzumab in patients with advanced or metastatic fibroblast activation protein-positive cancer. Clin Cancer Res. 2003;9(5):1639\u201347.","journal-title":"Clin Cancer Res"},{"issue":"11","key":"837_CR150","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.4161\/cbt.6.11.4874","volume":"6","author":"K Narra","year":"2007","unstructured":"Narra K, Mullins SR, Lee HO, et al. Phase II trial of single agent Val-boroPro (Talabostat) inhibiting fibroblast activation protein in patients with metastatic colorectal cancer. Cancer Biol Ther. 2007;6(11):1691\u20139.","journal-title":"Cancer Biol Ther"},{"issue":"7","key":"837_CR151","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1172\/JCI26532","volume":"116","author":"M Loeffler","year":"2006","unstructured":"Loeffler M, Kr\u00fcger JA, Niethammer AG, et al. Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. J Clin Invest. 2006;116(7):1955\u201362.","journal-title":"J Clin Invest"},{"issue":"5","key":"837_CR152","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1158\/1078-0432.CCR-17-2033","volume":"24","author":"EK Duperret","year":"2018","unstructured":"Duperret EK, Trautz A, Ammons D, et al. Alteration of the tumor stroma using a consensus DNA vaccine targeting fibroblast activation protein (FAP) synergizes with antitumor vaccine therapy in mice. Clin Cancer Res. 2018;24(5):1190\u2013201.","journal-title":"Clin Cancer Res"},{"key":"837_CR153","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.cellimm.2016.08.006","volume":"310","author":"Q Xia","year":"2016","unstructured":"Xia Q, Zhang FF, Geng F, et al. Improvement of anti-tumor immunity of fibroblast activation protein \u03b1 based vaccines by combination with cyclophosphamide in a murine model of breast cancer. Cell Immunol. 2016;310:89\u201398.","journal-title":"Cell Immunol"},{"issue":"6","key":"837_CR154","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1084\/jem.20130110","volume":"210","author":"E Tran","year":"2013","unstructured":"Tran E, Chinnasamy D, Yu Z, et al. Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia. J Exp Med. 2013;210(6):1125\u201335.","journal-title":"J Exp Med"},{"issue":"2","key":"837_CR155","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1158\/2326-6066.CIR-13-0027","volume":"2","author":"LC Wang","year":"2014","unstructured":"Wang LC, Lo A, Scholler J, et al. Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity. Cancer Immunol Res. 2014;2(2):154\u201366.","journal-title":"Cancer Immunol Res"},{"issue":"1","key":"837_CR156","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1186\/s12967-023-04080-z","volume":"21","author":"Y Liu","year":"2023","unstructured":"Liu Y, Sun Y, Wang P, et al. FAP-targeted CAR-T suppresses MDSCs recruitment to improve the antitumor efficacy of claudin18.2-targeted CAR-T against pancreatic cancer. J Transl Med. 2023;21(1):255.","journal-title":"J Transl Med"},{"key":"837_CR157","doi-asserted-by":"publisher","first-page":"1433679","DOI":"10.3389\/fimmu.2024.1433679","volume":"15","author":"W Niu","year":"2024","unstructured":"Niu W, Wang B, Zhang Y, et al. Efficacy and safety evaluation of cross-reactive fibroblast activation protein scFv-based CAR-T cells. Front Immunol. 2024;15:1433679.","journal-title":"Front Immunol"},{"issue":"1","key":"837_CR158","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.annonc.2020.10.474","volume":"32","author":"S Hiltbrunner","year":"2021","unstructured":"Hiltbrunner S, Britschgi C, Schuberth P, et al. Local delivery of CAR T cells targeting fibroblast activation protein is safe in patients with pleural mesothelioma: first report of FAPME, a phase I clinical trial. Ann Oncol. 2021;32(1):120\u201321.","journal-title":"Ann Oncol"},{"issue":"1","key":"837_CR159","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1186\/s40164-025-00691-y","volume":"14","author":"Y Wang","year":"2025","unstructured":"Wang Y, Zhang F, Qian Z, et al. Targeting collagen to optimize cancer immunotherapy. Exp Hematol Oncol. 2025;14(1):101.","journal-title":"Exp Hematol Oncol"},{"issue":"1","key":"837_CR160","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s40164-024-00591-7","volume":"14","author":"H Peng","year":"2025","unstructured":"Peng H, Chao Z, Wang Z, et al. Biomechanics in the tumor microenvironment: from biological functions to potential clinical applications. Exp Hematol Oncol. 2025;14(1):4.","journal-title":"Exp Hematol Oncol"},{"issue":"7","key":"837_CR161","doi-asserted-by":"publisher","first-page":"2909","DOI":"10.1073\/pnas.1018892108","volume":"108","author":"B Diop-Frimpong","year":"2011","unstructured":"Diop-Frimpong B, Chauhan VP, Krane S, et al. Losartan inhibits collagen I synthesis and improves the distribution and efficacy of nanotherapeutics in tumors. Proc Natl Acad Sci U S A. 2011;108(7):2909\u201314.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"837_CR162","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1038\/ncomms3516","volume":"4","author":"VP Chauhan","year":"2013","unstructured":"Chauhan VP, Martin JD, Liu H, et al. Angiotensin inhibition enhances drug delivery and potentiates chemotherapy by decompressing tumour blood vessels. Nat Commun. 2013;4:2516.","journal-title":"Nat Commun"},{"issue":"5","key":"837_CR163","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1016\/j.cell.2009.10.027","volume":"139","author":"KR Levental","year":"2009","unstructured":"Levental KR, Yu H, Kass L, et al. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell. 2009;139(5):891\u2013906.","journal-title":"Cell"},{"issue":"9","key":"837_CR164","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1038\/nm.2208","volume":"16","author":"V Barry-Hamilton","year":"2010","unstructured":"Barry-Hamilton V, Spangler R, Marshall D, et al. Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med. 2010;16(9):1009\u201317.","journal-title":"Nat Med"},{"issue":"3","key":"837_CR165","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1634\/theoncologist.2017-0024","volume":"22","author":"AB Benson","year":"2017","unstructured":"Benson AB, Wainberg ZA, Hecht JR, et al. A phase II randomized, double-blind, placebo-controlled study of simtuzumab or placebo in combination with gemcitabine for the first-line treatment of pancreatic adenocarcinoma. Oncologist. 2017;22(3):215\u201341.","journal-title":"Oncologist"},{"issue":"9","key":"837_CR166","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1038\/s43018-023-00614-y","volume":"4","author":"JL Chitty","year":"2023","unstructured":"Chitty JL, Yam M, Perryman L, et al. A first-in-class pan-lysyl oxidase inhibitor impairs stromal remodeling and enhances gemcitabine response and survival in pancreatic cancer. Nat Cancer. 2023;4(9):1326\u201344.","journal-title":"Nat Cancer"},{"issue":"3","key":"837_CR167","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.ccr.2012.01.007","volume":"21","author":"PP Provenzano","year":"2012","unstructured":"Provenzano PP, Cuevas C, Chang AE, et al. Enzymatic targeting of the stroma ablates physical barriers to treatment of pancreatic ductal adenocarcinoma. Cancer Cell. 2012;21(3):418\u201329.","journal-title":"Cancer Cell"},{"issue":"1","key":"837_CR168","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1136\/gutjnl-2012-302529","volume":"62","author":"MA Jacobetz","year":"2013","unstructured":"Jacobetz MA, Chan DS, Neesse A, et al. Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer. Gut. 2013;62(1):112\u201320.","journal-title":"Gut"},{"issue":"12","key":"837_CR169","doi-asserted-by":"publisher","first-page":"2848","DOI":"10.1158\/1078-0432.CCR-15-2010","volume":"22","author":"SR Hingorani","year":"2016","unstructured":"Hingorani SR, Harris WP, Beck JT, et al. Phase Ib study of PEGylated recombinant human hyaluronidase and gemcitabine in patients with advanced pancreatic cancer. Clin Cancer Res. 2016;22(12):2848\u201354.","journal-title":"Clin Cancer Res"},{"issue":"4","key":"837_CR170","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1200\/JCO.2017.74.9564","volume":"36","author":"SR Hingorani","year":"2018","unstructured":"Hingorani SR, Zheng L, Bullock AJ, et al. HALO 202: randomized phase II study of PEGPH20 plus nab-paclitaxel\/gemcitabine versus nab-paclitaxel\/gemcitabine in patients with untreated, metastatic pancreatic ductal adenocarcinoma. J Clin Oncol. 2018;36(4):359\u201366.","journal-title":"J Clin Oncol"},{"issue":"27","key":"837_CR171","doi-asserted-by":"publisher","first-page":"3185","DOI":"10.1200\/JCO.20.00590","volume":"38","author":"E Van Cutsem","year":"2020","unstructured":"Van Cutsem E, Tempero MA, Sigal D, et al. Randomized phase III trial of pegvorhyaluronidase alfa with nab-paclitaxel plus gemcitabine for patients with hyaluronan-high metastatic pancreatic adenocarcinoma. J Clin Oncol. 2020;38(27):3185\u201394.","journal-title":"J Clin Oncol"},{"issue":"7693","key":"837_CR172","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1038\/nature25501","volume":"554","author":"S Mariathasan","year":"2018","unstructured":"Mariathasan S, Turley SJ, Nickles D, et al. TGF\u03b2 attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018;554(7693):544\u201348.","journal-title":"Nature"},{"issue":"7693","key":"837_CR173","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/nature25492","volume":"554","author":"DVF Tauriello","year":"2018","unstructured":"Tauriello DVF, Palomo-Ponce S, Stork D, et al. TGF\u03b2 drives immune evasion in genetically reconstituted colon cancer metastasis. Nature. 2018;554(7693):538\u201343.","journal-title":"Nature"},{"key":"837_CR174","doi-asserted-by":"publisher","first-page":"1196970","DOI":"10.3389\/fimmu.2023.1196970","volume":"14","author":"T Li","year":"2023","unstructured":"Li T, Wang X, Niu M, et al. Bispecific antibody targeting TGF-\u03b2 and PD-L1 for synergistic cancer immunotherapy. Front Immunol. 2023;14:1196970.","journal-title":"Front Immunol"},{"issue":"1","key":"837_CR175","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1186\/s12964-024-01562-5","volume":"22","author":"T Li","year":"2024","unstructured":"Li T, Niu M, Zhou J, et al. The enhanced antitumor activity of bispecific antibody targeting PD-1\/PD-L1 signaling. Cell Commun Signal. 2024;22(1):179.","journal-title":"Cell Commun Signal"},{"issue":"12","key":"837_CR176","doi-asserted-by":"publisher","first-page":"e005543","DOI":"10.1136\/jitc-2022-005543","volume":"10","author":"M Yi","year":"2022","unstructured":"Yi M, Wu Y, Niu M, et al. Anti-TGF-\u03b2\/PD-L1 bispecific antibody promotes T cell infiltration and exhibits enhanced antitumor activity in triple-negative breast cancer. J Immunother Cancer. 2022;10(12):e005543.","journal-title":"J Immunother Cancer"},{"issue":"1","key":"837_CR177","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1186\/s13045-023-01487-5","volume":"16","author":"M Niu","year":"2023","unstructured":"Niu M, Yi M, Wu Y, et al. Synergistic efficacy of simultaneous anti-TGF-\u03b2\/VEGF bispecific antibody and PD-1 blockade in cancer therapy. J Hematol Oncol. 2023;16(1):94.","journal-title":"J Hematol Oncol"},{"issue":"1","key":"837_CR178","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s13045-021-01045-x","volume":"14","author":"M Yi","year":"2021","unstructured":"Yi M, Zhang J, Li A, et al. The construction, expression, and enhanced anti-tumor activity of YM101: a bispecific antibody simultaneously targeting TGF-\u03b2 and PD-L1. J Hematol Oncol. 2021;14(1):27.","journal-title":"J Hematol Oncol"},{"issue":"1","key":"837_CR179","doi-asserted-by":"publisher","first-page":"6315","DOI":"10.1038\/s41467-020-19920-5","volume":"11","author":"AL Grauel","year":"2020","unstructured":"Grauel AL, Nguyen B, Ruddy D, et al. TGF\u03b2-blockade uncovers stromal plasticity in tumors by revealing the existence of a subset of interferon-licensed fibroblasts. Nat Commun. 2020;11(1):6315.","journal-title":"Nat Commun"},{"issue":"10","key":"837_CR180","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1038\/s41416-018-0246-z","volume":"119","author":"D Melisi","year":"2018","unstructured":"Melisi D, Garcia-Carbonero R, Macarulla T, et al. Galunisertib plus gemcitabine vs. gemcitabine for first-line treatment of patients with unresectable pancreatic cancer. Br J Cancer. 2018;119(10):1208\u201314.","journal-title":"Br J Cancer"},{"issue":"5933","key":"837_CR181","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1126\/science.1171362","volume":"324","author":"KP Olive","year":"2009","unstructured":"Olive KP, Jacobetz MA, Davidson CJ, et al. Inhibition of hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer. Science. 2009;324(5933):1457\u201361.","journal-title":"Science"},{"issue":"6","key":"837_CR182","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/j.ccr.2014.04.021","volume":"25","author":"AD Rhim","year":"2014","unstructured":"Rhim AD, Oberstein PE, Thomas DH, et al. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma. Cancer Cell. 2014;25(6):735\u201347.","journal-title":"Cancer Cell"},{"issue":"36","key":"837_CR183","doi-asserted-by":"publisher","first-page":"4284","DOI":"10.1200\/JCO.2015.62.8719","volume":"33","author":"DV Catenacci","year":"2015","unstructured":"Catenacci DV, Junttila MR, Karrison T, et al. Randomized phase Ib\/II study of gemcitabine plus placebo or vismodegib, a hedgehog pathway inhibitor, in patients with metastatic pancreatic cancer. J Clin Oncol. 2015;33(36):4284\u201392.","journal-title":"J Clin Oncol"},{"issue":"1","key":"837_CR184","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1093\/jnci\/djx121","volume":"110","author":"CJ Hanley","year":"2018","unstructured":"Hanley CJ, Mellone M, Ford K, et al. Targeting the myofibroblastic cancer-associated fibroblast phenotype through inhibition of NOX4. J Natl Cancer Inst. 2018;110(1):109\u201320.","journal-title":"J Natl Cancer Inst"},{"issue":"9","key":"837_CR185","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1158\/0008-5472.CAN-19-3158","volume":"80","author":"K Ford","year":"2020","unstructured":"Ford K, Hanley CJ, Mellone M, et al. NOX4 inhibition potentiates immunotherapy by overcoming cancer-associated fibroblast-mediated CD8 T-cell exclusion from tumors. Cancer Res. 2020;80(9):1846\u201360.","journal-title":"Cancer Res"},{"issue":"1","key":"837_CR186","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41392-025-02347-z","volume":"10","author":"J Amengual","year":"2025","unstructured":"Amengual J, Gonzalez-Sanchez E, Y\u00e1\u00f1ez-Bartolome M, et al. NADPH oxidase 1\/4 dual inhibition impairs transforming growth factor-beta protumorigenic effects in cholangiocarcinoma cancer-associated fibroblasts. Signal Transduct Target Ther. 2025;10(1):257.","journal-title":"Signal Transduct Target Ther"},{"issue":"Suppl 2","key":"837_CR187","doi-asserted-by":"publisher","first-page":"S615","DOI":"10.1016\/j.annonc.2024.08.914","volume":"35","author":"J Fayette","year":"2024","unstructured":"Fayette J, et al. Setanaxib plus pembrolizumab for the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck: results of a randomized, double-blind phase II trial. Ann Oncol. 2024;35(Suppl 2):S615.","journal-title":"Ann Oncol"},{"issue":"1","key":"837_CR188","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1038\/nrclinonc.2016.60","volume":"14","author":"UE Martinez-Outschoorn","year":"2017","unstructured":"Martinez-Outschoorn UE, Peiris-Pag\u00e9s M, Pestell RG, et al. Cancer metabolism: a therapeutic perspective. Nat Rev Clin Oncol. 2017;14(1):11\u201331.","journal-title":"Nat Rev Clin Oncol"},{"issue":"2","key":"837_CR189","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1038\/s41573-021-00339-6","volume":"21","author":"ZE Stine","year":"2022","unstructured":"Stine ZE, Schug ZT, Salvino JM, et al. Targeting cancer metabolism in the era of precision oncology. Nat Rev Drug Discov. 2022;21(2):141\u201362.","journal-title":"Nat Rev Drug Discov"},{"issue":"1","key":"837_CR190","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1038\/s41392-021-00641-0","volume":"6","author":"F Wu","year":"2021","unstructured":"Wu F, Yang J, Liu J, et al. Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer. Signal Transduct Target Ther. 2021;6(1):218.","journal-title":"Signal Transduct Target Ther"},{"issue":"7","key":"837_CR191","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/s41571-019-0203-7","volume":"16","author":"X Li","year":"2019","unstructured":"Li X, Wenes M, Romero P, et al. Navigating metabolic pathways to enhance antitumour immunity and immunotherapy. Nat Rev Clin Oncol. 2019;16(7):425\u201341.","journal-title":"Nat Rev Clin Oncol"},{"issue":"5","key":"837_CR192","doi-asserted-by":"publisher","first-page":"90","DOI":"10.3892\/ijo.2025.5796","volume":"67","author":"R Li","year":"2025","unstructured":"Li R, Li Y. Role of metabolic reprogramming of cancer-associated fibroblasts in tumor development and progression. Int J Oncol. 2025;67(5):90.","journal-title":"Int J Oncol"},{"issue":"4","key":"837_CR193","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/s43018-026-01146-x","volume":"7","author":"S Pramod","year":"2026","unstructured":"Pramod S, Lavon H, Scherz-Shouval R, et al. Heterogeneity and plasticity of cancer-associated fibroblasts. Nat Cancer. 2026;7(4):583\u201396.","journal-title":"Nat Cancer"}],"container-title":["Experimental Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-026-00837-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40164-026-00837-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-026-00837-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T23:05:30Z","timestamp":1791673530000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40164-026-00837-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,10]]},"references-count":193,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["837"],"URL":"https:\/\/doi.org\/10.1186\/s40164-026-00837-6","relation":{},"ISSN":["2162-3619"],"issn-type":[{"value":"2162-3619","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,10]]},"assertion":[{"value":"18 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Not applicable.","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"104"}}