癌症相关成纤维细胞作为胃肠道肿瘤中获得性免疫豁免样生态位的构建者：来自眼部免疫豁免与屏障生物学的启示

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.