MINI REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1668535
This article is part of the Research TopicTargeting cancer-associated fibroblasts: Disrupting immune evasion and therapy resistanceView all 6 articles
Cancer-Associated Fibroblasts in Osteosarcoma: Key Players in Immune Escape and Targeted Therapy
Provisionally accepted
- Suzhou Ninth People's Hospital, Suzhou, China
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Osteosarcoma represents the most common principal malignant bone tumor that predominantly appears among teenagers and children. While multimodal treatment methods have greatly evolved with time, survival for recurrent or metastatic disease remains low due to the resistance that accumulates during treatment. Increasing evidence identifies the tumor microenvironment (TME), in particular cancer-associated fibroblasts (CAFs), as playing an important role in imposing immune suppression, enhancing tumor aggressiveness, and mediating resistance toward immunotherapy and chemotherapy. This article gives an overview of the derivation, phenotypic heterogeneity, and mechanisms of action of CAFs during osteosarcoma, such as facilitating immune escape, survival signaling, drug efflux, regulation of genes through exosomes, and inhibiting ferroptosis. Furthermore, we present existing and new treatment methods that are centered on CAFs, such as suppression of the paracrine pathway (e.g., IL-6/STAT3, TGF-β), depletion of CAFs lineages by targeting fibroblast activation protein (FAP), and conversion toward tumor-restraining CAFs. Other methods that are gaining popularity are targeting CAFs-releasing exosomes and metabolic liabilities. By shedding light on CAFs-based methods for imposing resistance and trying targeted treatments, this review offers insights into novel therapeutic combinations that can overcome treatment barriers and improve survival outcomes in osteosarcoma regimens.
Keywords: Osteosarcoma, cancer-associated fibroblasts, Immune Evasion, therapy resistance, Tumor Microenvironment
Received: 18 Jul 2025; Accepted: 07 Aug 2025.
Copyright: © 2025 Fan, Jin, Lv, Wu, Li and Wang. 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: Churong Wang, Suzhou Ninth People's Hospital, Suzhou, China
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