Pawar Jogendra Singh, Salam Md Abdus, Dipto Md Shalman Uddin, Al-Amin Md Yusuf, Salam Moushumi Tabassoom, Sengupta Sagnik, Kumari Smita, Gujjari Lohitha, Yadagiri Ganesh
Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
The James Cancer Hospital and Solove Research Institute, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Cancers (Basel). 2025 Jul 28;17(15):2484. doi: 10.3390/cancers17152484.
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.
癌症不再被视为一个孤立的事件。相反，它的发生是由于一种复杂的生物学驱动力，这种驱动力协调肿瘤微环境（TME）内的不同细胞类型、生长因子、细胞因子和信号通路。癌症相关成纤维细胞（CAFs）是TME复杂生态系统中数量最多的基质细胞，其起源和功能表型具有显著的异质性和可塑性。作为非常神秘的细胞，CAFs通过与TME中不同的肿瘤浸润免疫细胞进行广泛的相互信号传导来决定肿瘤的进展和结局。在其生物学驱动过程中，CAFs释放大量化学介质，并利用各种信号通路来招募和调节肿瘤浸润免疫细胞。CAF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创造了一个免疫抑制性TME，阻碍肿瘤细胞对肿瘤浸润淋巴细胞（TILs）的敏感性。此外，通过沉积和重塑细胞外基质（ECM），CAFs重塑TME，从而促进肿瘤生长、侵袭、转移和化疗耐药性。了解CAF生物学及其与肿瘤浸润免疫细胞的相互作用不仅对于深入了解肿瘤发生至关重要，而且对于优化新型癌症靶向免疫疗法的潜力也至关重要。CAFs与肿瘤浸润免疫细胞之间的复杂关系仍不清楚，需要进一步研究。在此，在这篇叙述性综述中，我们重点关注了CAF生物学的最新进展及其与肿瘤浸润免疫细胞在产生免疫抑制性TME和细胞死亡抗性方面的相互作用。
