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肿瘤相关成纤维细胞(CAFs)调控CD8⁺T细胞浸润的研究进展

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

  • 摘要: 肿瘤相关成纤维细胞(CAFs)是肿瘤微环境中的核心调控者,其高度异质性与可塑性深刻影响CD8⁺T细胞的浸润与功能,从而决定免疫治疗响应。本文系统综述CAF不同亚群(包括肌成纤维细胞样、炎症性、抗原呈递性及代谢重组型CAFs)在动态演变过程中调控CD8⁺T细胞浸润的多维度机制,涵盖细胞外基质重塑、免疫抑制因子分泌、代谢重编程、血管正常化以及与免疫细胞互作等。通过进一步整合单细胞与空间多组学视角,提出CAF免疫调控网络的概念,并总结靶向CAF的治疗策略(如TGF-β抑制、FAP靶向、CAF重编程等)及其与免疫检查点抑制剂的协同潜力。最后,展望未来研究方向,包括开发CAF特异性递送系统、构建类器官模型、结合人工智能预测治疗响应等,为突破免疫治疗耐药提供新思路。

     

    Abstract: 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.

     

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