Cancer is no longer considered as an isolated event. Rather, it occurs because of a complex biological drive orchestrating different cell types, growth factors, cytokines, and signaling pathways within the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs) are the most populous stromal cells within the complex ecosystem of TME, with significant heterogeneity and plasticity in origin and functional phenotypes. Very enigmatic cells, CAFs determine the progress and outcomes of tumors through extensive reciprocal signaling with different tumors infiltrating immune cells in the TME. In their biological drive, CAFs release numerous chemical mediators and utilize various signaling pathways to recruit and modulate tumor-infiltrating immune cells. The CAF-induced secretome and exosomes render immune cells ineffective for their antitumor activities. Moreover, by upregulating immune inhibitory checkpoints, CAFs create an immunosuppressive TME that impedes the susceptibility of tumor cells to tumor-infiltrating lymphocytes (TILs). Further, by depositing and remodeling extracellular matrix (ECM), CAFs reshape the TME, which enhances tumor growth, invasion, metastasis, and chemoresistance. Understanding of CAF biology and its crosstalk with tumor-infiltrating immune cells is crucial not only to gain insight in tumorigenesis but to optimize the potential of novel targeted immunotherapies for cancers. The complex relationships between CAFs and tumor-infiltrating immune cells remain unclear and need further study. Herein, in this narrative review we have focused on updates of CAF biology and its interactions with tumor-infiltrating immune cells in generating immunosuppressive TME and resistance to cell death.
癌症不再被视为孤立事件，其发生源于肿瘤微环境（TME）中多种细胞类型、生长因子、细胞因子及信号通路共同构成的复杂生物学驱动机制。癌症相关成纤维细胞（CAFs）作为TME复杂生态系统中最丰富的间质细胞，在起源与功能表型上具有显著的异质性和可塑性。这类高度复杂的细胞通过与TME中不同肿瘤浸润免疫细胞进行广泛的双向信号传导，深刻影响着肿瘤的进展与结局。在其生物学驱动过程中，CAFs释放大量化学介质并利用多种信号通路招募和调控肿瘤浸润免疫细胞。CAFs诱导的分泌组和外泌体使免疫细胞的抗肿瘤活性失效。此外，通过上调免疫抑制检查点，CAFs构建了抑制性的肿瘤微环境，阻碍肿瘤细胞对肿瘤浸润淋巴细胞（TILs）的敏感性。同时，CAFs通过沉积和重塑细胞外基质（ECM）改变TME结构，从而促进肿瘤生长、侵袭、转移及化疗耐药。深入理解CAFs的生物学特性及其与肿瘤浸润免疫细胞的相互作用，不仅对揭示肿瘤发生机制至关重要，更能为优化新型癌症靶向免疫疗法的潜力提供关键依据。目前CAFs与肿瘤浸润免疫细胞间的复杂关系尚未完全阐明，仍需进一步探索。本综述系统阐述了CAFs生物学研究的最新进展，重点探讨其在构建免疫抑制性TME及诱导细胞死亡抵抗过程中与肿瘤浸润免疫细胞的相互作用机制。
肿瘤(癌症)患者之家