PERSPECTIVE article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicUsing Oncolytic Viruses in Cancer Immunity and Immunotherapy: Hepatocellular Carcinoma, Gastric Cancer, and Colorectal CancerView all 3 articles
Oncolytic Virus Therapy for Osteosarcoma: Mechanisms, Opportunities, and Challenges
Provisionally accepted
- 1The Fourth Hospital of Heibei Medical University, Shijiazhuang, China
- 2China Academy of Chinese Medical Sciences Wangjing Hospital, Beijing, China
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Osteosarcoma (OS), the most common primary malignant bone tumor in children and adolescents, remains a major therapeutic challenge due to its high metastatic potential and limited response to conventional treatments, including immune checkpoint inhibitors (ICIs). Oncolytic viruses (OVs) have emerged as a promising strategy with dual antitumor functions: direct oncolysis and the induction of immunogenic cell death (ICD). By releasing damage-associated molecular patterns (DAMPs) and activating the cGAS–STING pathway, OVs can remodel the immunologically "cold" tumor microenvironment (TME) into an inflamed and immune-responsive phenotype, thereby enhancing CD8⁺ T-cell infiltration and improving antitumor immunity. Encouraging preclinical evidence has been reported: VSV-IFNβ-NIS achieved a long-term survival rate of approximately 35% in canine OS models, and synergistic combination regimens have demonstrated tumor inhibition rates exceeding 70%. Despite these advances, OV-based therapies still face critical translational challenges, including the immunosuppressive TME, intratumoral delivery barriers, and safety concerns. This review systematically summarizes the molecular mechanisms underlying OV-mediated antitumor immunity, evaluates current clinical evidence, and highlights future opportunities, such as combination immunotherapy, mesenchymal stem cell (MSC)-based delivery platforms, and AI-driven precision medicine approaches. Our goal is to provide a comprehensive theoretical framework to support the clinical translation and personalized application of OV therapy in osteosarcoma.
Keywords: oncolytic virus, Osteosarcoma, Immunogenic cell death, Tumor Microenvironment, precision medicine
Received: 14 Oct 2025; Accepted: 26 Nov 2025.
Copyright: © 2025 Wang, Ge, Liu 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: Xiaoyu Zhang
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