{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:54:13Z","timestamp":1791186853132,"version":"4.1.0"},"reference-count":318,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100025294","name":"Research Ireland","doi-asserted-by":"publisher","award":["FFP\/19\/6446"],"award-info":[{"award-number":["FFP\/19\/6446"]}],"id":[{"id":"10.13039\/501100025294","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"abstract":"Abstract<\/jats:title>\n \n Although substantial advances have been made in cancer immunotherapy, the immunosuppressive tumour microenvironment (TME) continues to pose a significant obstacle to the achievement of sustained clinical responses. Cancer\u2010associated fibroblasts (CAFs) are increasingly recognised as pivotal regulators in the TME. Their functional adaptability shapes immune responses through extracellular matrix (ECM) remodelling, metabolic reprogramming and the secretion of immunomodulatory factors. This review explores the heterogeneity and plasticity of CAFs, characterising them as dynamic functional states, including myofibroblastic (myCAF), inflammatory (iCAF), antigen\u2010presenting (apCAF) phenotypes and hypoxia\u2010induced senescent fibroblasts (hsCAF), which transition fluidly in response to microenvironmental cues and oncogenic signalling. Through a comparative analysis of colorectal cancer (CRC) and multiple myeloma (MM), this review highlights how stromal regulation is adaptive across solid and haematological malignancies. In CRC, CAFs establish dense, collagen\u2010rich ECM barriers that exclude effector T cells, whereas, in MM, they establish adhesion\u2010dependent niches within the bone marrow to spatially segregate immune cells from malignant plasma cells. This review also discusses how oncogenic drivers such as KRAS and TP53 \u2018educate\u2019 the stromal microenvironment and explores emerging immune evasion mechanisms, including the sialic acid\u2010Siglec glyco\u2010immune checkpoint. Current therapeutic approaches are shifting from non\u2010selective stromal depletion toward normalising phenotypes, blocking secretome factors and disrupting metabolic interactions. The integration of spatial multi\u2010omics and artificial intelligence provides a framework for mapping these functional landscapes. In conclusion, harnessing CAF heterogeneity in multimodal combination therapies may help shift the tumour microenvironment from an immunosuppressive to a more pro\u2010immune state.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>","DOI":"10.1113\/jp291166","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T07:22:16Z","timestamp":1791184936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cancer\u2010associated fibroblast heterogeneity across solid and haematological malignancies: Lessons from colorectal cancer and multiple myeloma"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-7781-8913","authenticated-orcid":false,"given":"Hui","family":"Mo","sequence":"first","affiliation":[{"name":"Discipline of Advanced Therapies, School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"Discipline of Pharmacology and Therapeutics, School of Pharmacy and Medical Sciences, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1984-7036","authenticated-orcid":false,"given":"Haoyan","family":"Han","sequence":"additional","affiliation":[{"name":"Discipline of Advanced Therapies, School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"Discipline of Pharmacology and Therapeutics, School of Pharmacy and Medical Sciences, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6173-7140","authenticated-orcid":false,"given":"Michael","family":"O'Dwyer","sequence":"additional","affiliation":[{"name":"Discipline of Advanced Therapies, School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"C\u00daRAM Centre for Research in Medical Devices, School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"Rinn Advanced Therapies School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5562-5241","authenticated-orcid":false,"given":"Eileen","family":"Reidy","sequence":"additional","affiliation":[{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"C\u00daRAM Centre for Research in Medical Devices, School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"School of Biological and Chemical Sciences, College of Science and engineering University of Galway Galway Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5831-6783","authenticated-orcid":false,"given":"Aideen E.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Discipline of Advanced Therapies, School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"Discipline of Pharmacology and Therapeutics, School of Pharmacy and Medical Sciences, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"Lambe Institute for Translational Research, School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"C\u00daRAM Centre for Research in Medical Devices, School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"},{"name":"Rinn Advanced Therapies School of Medicine, College of Medicine, Nursing and Health Sciences University of Galway Galway Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"issue":"5","key":"e_1_2_2_2_1","doi-asserted-by":"crossref","first-page":"3918","DOI":"10.1002\/jcp.30135","article-title":"Mesenchymal stem cells induce PD\u2010L1 expression through the 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