MINI REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1621521
This article is part of the Research TopicTargeting cancer-associated fibroblasts: Disrupting immune evasion and therapy resistanceView all 5 articles
The malignant dialogue between cancer-associated fibroblasts and osteosarcoma cells: Microenvironment-mediated drug resistance and therapeutic targets
Provisionally accepted
- 1Zhuji People's Hospital of Zhejiang Province, Shaoxing, China
- 2Naval Medical University, Shanghai, China
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Cancer-associated fibroblasts (CAFs) are pivotal in shaping the immunosuppressive and chemoresistant tumor microenvironment (TME) of osteosarcoma (OS). This review explores how CAFs drive OS progression through paracrine signaling (e.g., TGF-β, IL-6), extracellular matrix (ECM) remodeling, exosome-mediated crosstalk, and metabolic reprogramming. We highlight CAF heterogeneity (e.g., myCAFs, iCAFs) and their roles in therapy resistance, emphasizing emerging strategies such as FAP inhibitors, TGF-β blockers, and CXCR4 antagonists. Combining these approaches with immunotherapy or chemotherapy offers promise for overcoming chemoresistance. Challenges like CAF plasticity and biomarker development are discussed, alongside future directions for precision targeting in OS.
Keywords: Osteosarcoma, cancer-associated fibroblasts, chemoresistance, Extracellular Matrix, Tumor Microenvironment
Received: 01 May 2025; Accepted: 31 Jul 2025.
Copyright: © 2025 Wang, Luo and Zhang. 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: Danying Zhang, Naval Medical University, Shanghai, China
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