REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1635771
Cancer-Associated Fibroblasts: Dual Roles from Senescence Sentinels to Death Regulators and New Dimensions in Therapy
Provisionally accepted
- 1Shanghai Cancer Center, Fudan University, Shanghai, China
- 2East China University of Science and Technology, Shanghai, China
- 3The Second Affiliated Hospital of Zhejiang University School of Medicine Linping Campus, Hangzhou, China
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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 anticancer strategies.
Keywords: cancer-associated fibroblasts, cell senescence, Cell Death, SASP, TME
Received: 27 May 2025; Accepted: 02 Jul 2025.
Copyright: © 2025 Guo, Ruan, Wang and Ou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Duancheng Guo, Shanghai Cancer Center, Fudan University, Shanghai, China
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