Ruan Guixiang, Wang Xiang, Ou Huiyi, Guo Duancheng
Department of Radiology, First People's Hospital of Linping District, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Front Immunol. 2025 Jul 18;16:1635771. doi: 10.3389/fimmu.2025.1635771. eCollection 2025.
Cancer-associated fibroblasts (CAFs) are critical components of the tumor microenvironment (TME), playing a pivotal role in tumor initiation, progression, and therapeutic resistance. This review explores the dual roles of CAFs in regulating tumor cell senescence and cell death, elucidating their mechanisms in inducing cellular senescence, shaping an immunosuppressive milieu, and modulating cell death pathways. CAFs promote tumor progression by secreting pro-inflammatory factors and extracellular matrix (ECM) components, while also contributing to metabolic reprogramming, immune evasion, and therapy resistance, thereby influencing anti-cancer treatment efficacy. Studies indicate that the heterogeneity and plasticity of CAFs determine their distinct functions across various tumor types. Consequently, precision-targeted therapeutic strategies against CAFs, including the elimination of senescent CAFs, inhibition of the senescence-associated secretory phenotype (SASP), and disruption of CAF-mediated cell death evasion mechanisms, have emerged as promising directions in cancer research. This review provides a comprehensive analysis of CAFs functions and their potential as therapeutic targets, offering valuable insights into the development of novel anti-cancer strategies.
癌症相关成纤维细胞（CAFs）是肿瘤微环境（TME）的关键组成部分，在肿瘤的起始、进展和治疗耐药性中发挥着关键作用。本综述探讨了CAFs在调节肿瘤细胞衰老和细胞死亡中的双重作用，阐明了它们在诱导细胞衰老、塑造免疫抑制环境以及调节细胞死亡途径中的机制。CAFs通过分泌促炎因子和细胞外基质（ECM）成分促进肿瘤进展，同时也参与代谢重编程、免疫逃逸和治疗耐药性，从而影响抗癌治疗效果。研究表明，CAFs的异质性和可塑性决定了它们在不同肿瘤类型中的独特功能。因此，针对CAFs的精准靶向治疗策略，包括消除衰老的CAFs、抑制衰老相关分泌表型（SASP）以及破坏CAF介导的细胞死亡逃避机制，已成为癌症研究中很有前景的方向。本综述对CAFs的功能及其作为治疗靶点的潜力进行了全面分析，为新型抗癌策略的开发提供了有价值的见解。
