{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T23:51:56Z","timestamp":1794009116335,"version":"4.8.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Gastrointestinal cancers frequently develop immune exclusion and therapeutic resistance, yet these phenotypes are often described separately. Cancer-associated fibroblasts (CAFs) are key stromal architects of immune-excluded tumor microenvironments, and their heterogeneous states can evolve under chemotherapy, radiotherapy, immunotherapy, targeted therapy, and anti-angiogenic pressure. We propose that treatment-induced injury, inflammation, hypoxia, and repair signals reshape CAFs. These therapy-educated CAFs can construct acquired immune-privileged-like niches by integrating extracellular matrix remodeling, immunosuppressive secretomes, vascular-barrier remodeling, and spatial exclusion of cytotoxic immune cells. Ocular barrier biology offers a conceptual, not anatomical, analog for this spatial organization. In gastrointestinal tumors, these principles may be pathologically co-opted by myCAF-, iCAF-, and apCAF-like programs to restrict CD8+ T-cell and NK-cell access, recruit suppressive myeloid and regulatory populations, and impair drug delivery. This framework may guide spatial multiomics, digital pathology, radiomics, CAF-derived biomarkers, and spatially guided CAF reprogramming strategies. It also provides falsifiable questions for paired pre- and post-treatment sampling across gastrointestinal cancer types.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1946857","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T05:34:31Z","timestamp":1787636071000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Cancer-associated fibroblasts as architects of acquired immune-privileged-like niches in gastrointestinal cancers: lessons from ocular immune privilege and barrier biology"],"prefix":"10.3389","volume":"17","author":[{"given":"Yingjian","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated 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