肿瘤防治研究2026，Vol.53Issue(8)：625-632,8.DOI:10.3971/j.issn.1000-8578.2026.25.0955
肿瘤相关成纤维细胞调控CD8+T细胞浸润的研究进展
Research Progress on Regulation of CD8+T Cell Infiltration by Cancer-Associated Fibroblasts
摘要
Abstract
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.关键词
CAFs/CD8+T细胞/癌种特异性/免疫排斥分型/冷肿瘤/靶向治疗Key words
CAFs/CD8+T cells/Cancer type-specificity/Immune exclusion subtype/Cold tumor/Targeted therapy分类
医药卫生引用本文复制引用
张鹏飞,邵彩玲,姬菩忠,杨艳丽..肿瘤相关成纤维细胞调控CD8+T细胞浸润的研究进展[J].肿瘤防治研究,2026,53(8):625-632,8.基金项目
Health Industry Research Project of Gansu Province(No.GSWSKY2024-59) （No.GSWSKY2024-59）
The Intra-hospital Project of The 940th Hospital of Joint Logistic Support Force of Chinese People's Liberation Army(No.2021yxky049) 甘肃省卫生健康行业科研项目(GSWSKY-2024-59) （No.2021yxky049）
中国人民解放军联勤保障部队第九四〇医院内课题(2021yxky049) （2021yxky049）
