MINI REVIEW article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1702219
This article is part of the Research TopicExploring immune low-response states through single-cell technologies and spatial transcriptomicsView all 27 articles
Decoding the Immune Microenvironment in Osteosarcoma: New Insights into Checkpoints, Vaccines, and CAR-T Cells
Provisionally accepted
- 1China-Japan Union Hospital of Jilin University, Department of Traumatic Orthopedics, Changchun 130033, China, Changchun, China
- 2Changchun University of Chinese Medicine, Changchun, China
- 3Department of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanbian 133000, China, Yanbian, China
- 4Changchun University of Chinese Medicine, Changchun 130117, China, Changchun, China
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Osteosarcoma (OS), the most prevalent primary malignant bone tumor, disproportionately affects adolescents and is marked by rapid progression and a high rate of pulmonary metastasis. Despite advances in multimodal treatment, outcomes remain dismal for metastatic or relapsed disease, largely due to chemoresistance, immune evasion, and the heterogeneous tumor microenvironment (TME). Increasing evidence underscores the immunoregulatory complexity of osteosarcoma, characterized by immunosuppressive myeloid-derived populations, dysfunctional lymphocyte infiltration, and exosome-mediated immune escape. While immune checkpoint inhibitors have revolutionized treatment in several malignancies, their impact in osteosarcoma remains modest, highlighting the need for combinatorial strategies. Emerging approaches such as adoptive T cell therapies, tumor vaccines, and CAR-T cell interventions are being explored to overcome the "cold" immune milieu. Furthermore, single-cell transcriptomics has shed light on cellular interactions within the osteosarcoma TME, offering insights into resistance mechanisms and potential biomarkers. This review provides a comprehensive overview of the immunological landscape of osteosarcoma and highlights current and emerging immunotherapeutic strategies aimed at improving clinical outcomes in this challenging malignancy.
Keywords: Osteosarcoma, Tumor Microenvironment, Immunosuppression, immune checkpoint inhibitors, Immunotherapy, Combinatorial approaches
Received: 09 Sep 2025; Accepted: 16 Oct 2025.
Copyright: © 2025 Wang, Tongtong, Yang, Xu, Zhang, Liu and Ren. 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:
Guangyao Liu, gyliu@jlu.edu.cn
Hongge Ren, 2563835546@qq.com
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