肿瘤相关成纤维细胞调控CD8+T细胞浸润的研究进展OA

Cancer-associated fibroblasts(CAFs)are core regulators in the tumor microenvironment.Their high heterogeneity and plasticity remarkably influence the infiltration and function of CD8+T cells,thereby determining the response to immunotherapy.However,the mechanisms by which CAFs impede CD8+T cell infiltration exhibit substantial heterogeneity across different cancer types.This review proposes a dichotomous model of CAFs-mediated immune exclusion:Type Ⅰ active exclusion(exemplified by pancreatic ductal adenocarcinoma,where CAFs create physical and chemical barriers through excessive extracellular matrix deposition and secretion of TGF-β/CXCL12)and Type Ⅱ immune ignorance(exemplified by a subset of microsatellite-stable colorectal cancers,where loss of CAFs function results in insufficient chemokine production).Under this framework,we systematically review the specific regulatory mechanisms of CAFs subsets,specifically myofibroblastic CAFs and inflammatory CAFs,in pancreatic cancer,triple-negative breast cancer,non-small cell lung cancer,and colorectal cancer,highlighting their multidimensional roles in extracellular matrix remodeling,metabolic reprogramming,and construction of immunosuppressive networks.Furthermore,by integrating single-cell and spatial multi-omics perspectives,we propose immune phenotype-based CAFs-targeting strategies,namely,"barrier-breaking"strategies(TGF-β inhibition and FAP targeting)for Type Ⅰ tumors and"activating"strategies(reprogramming CAFs toward an immune-supportive phenotype)for Type Ⅱ tumors,and discuss their temporally sequenced combination with immune checkpoint inhibitors.