Research progress on the regulation of CD8+ T cell infiltration by cancer-associated fibroblasts (CAFs)

Cancer-associated fibroblasts (CAFs) are core regulators in the tumor microenvironment (TME). Their high heterogeneity and plasticity profoundly influence the infiltration and function of CD8⁺ T cells, thereby determining the response to immunotherapy. This review systematically summarizes the multi-dimensional mechanisms by which distinct CAF subsets (including myofibroblast-like, inflammatory, antigen-presenting, and metabolically reprogrammed CAFs) regulate CD8⁺ T cell infiltration during their dynamic evolution. These mechanisms encompass extracellular matrix remodeling, secretion of immunosuppressive factors, metabolic reprogramming, vascular normalization, and crosstalk with immune cells. By further integrating single-cell and spatial multi-omics perspectives, we propose the concept of a CAF-mediated immunoregulatory network, and summarize CAF-targeted therapeutic strategies (such as TGF-β inhibition, FAP targeting, and CAF reprogramming) as well as their synergistic potential with immune checkpoint inhibitors (ICIs). Finally, we prospect future research directions, including the development of CAF-specific delivery systems, construction of organoid models, and application of artificial intelligence-based prediction of treatment responses, aiming to provide novel insights for overcoming immunotherapy resistance.