Research Progress on Regulation of CD8+ T Cell Infiltration by Cancer-Associated Fibroblasts
10.3971/j.issn.1000-8578.2026.25.0955
- VernacularTitle:肿瘤相关成纤维细胞调控CD8+ T细胞浸润的研究进展
- Author:
Pengfei ZHANG
1
;
Cailing SHAO
1
;
Puzhong JI
2
;
Yanli YANG
1
Author Information
1. Pathology Department, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730000, China;First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou 730000, China.
2. Pathology Department, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730000, China.
- Publication Type:REVIEWS
- Keywords:
CAFs;
CD8+ T cells;
Cancer type-specificity;
Immune exclusion subtype;
Cold tumor;
Targeted therapy
- From:
Cancer Research on Prevention and Treatment
2026;53(8):625-632
- CountryChina
- Language:Chinese
-
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.
