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REVIEW ARTICLE

Immunotherapy in bone and soft-tissue tumors: Current advances and future directions

Li Fang1 ,  Chong Zheng2,3 ,  Haijun Tang4 ,  Jian Li1 ,  Haohong Zheng1 ,  Bin Yang3 ,  Xiaodan Li2,3* ,  Jian Wang2* ,  Jianlong Li2*
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1 Department of Orthopedics, First Affiliated Hospital, Jinzhou Medical University, Jinzhou, Liaoning, China
2 Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
3 Department of Orthopedics, Zengcheng Courtyard of Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
4 Department of Spine Surgery, Center for Orthopaedic Surgery, Academy of Orthopedics, Orthopaedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China
OTE, 025360015 https://doi.org/10.36922/OTE025360015
Received: 1 September 2025 | Revised: 5 December 2025 | Accepted: 22 December 2025 | Published online: 20 February 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Immunotherapy has emerged as a transformative strategy for treating bone and soft-tissue sarcomas, a class of rare, heterogeneous malignancies originating from mesenchymal tissues; however, significant challenges remain. This narrative review summarizes recent advances in sarcoma immunotherapy, covering molecular mechanisms, tumor microenvironment (TME) characteristics, and treatment responses specific to major subtypes such as osteosarcoma, liposarcoma, and synovial sarcoma. Notably, despite being a distinct myeloid neoplasm rather than a sarcoma, systemic mastocytosis is included in this study to identify common therapeutic targets through cross-disease comparisons (e.g., kinase-driven pathways and mechanisms regulating the immunosuppressive TME). Clinical data indicate that single-agent immune checkpoint inhibitors (ICIs) produce limited objective response rates in advanced sarcomas (approximately 16.7%), with significant efficacy disparities across subtypes, ranging from high response rates in alveolar soft part sarcomas to minimal responses in osteosarcomas. Key resistance mechanisms include a suppressive TME dominated by myeloid-derived suppressor cells, low tumor mutational burden, and antigenic heterogeneity. Combination strategies such as ICIs with radiotherapy, tyrosine kinase inhibitors, or anti-angiogenic agents significantly improve outcomes. Emerging cell therapies such as chimeric antigen receptor T-cell, T-cell receptor–engineered, and tumor-infiltrating lymphocyte therapies, combined with neoantigen vaccines and nanotechnology-driven delivery systems, demonstrate potential in reshaping the TME and overcoming immune escape. Biomarkers, including programmed death-ligand 1 expression, tertiary lymphoid structures, and immune gene profiles, hold prognostic value but require further validation. Future research should prioritize tissue-specific trial designs, combined TME remodeling regimens, and biomarker-guided personalized therapies to effectively convert “cold” sarcomas into immunotherapy-responsive malignancies.

Keywords
Bone and soft-tissue tumor
Combination immunotherapy
Tumor microenvironment
Funding
The authors gratefully acknowledge the support from the National Natural Science Foundation of China (82573295), GuangDong Basic and Applied Basic Research Foundation (2024A1515030050), and Research Fund of Nanfang Hospital, Southern Medical University (2023A031).
Conflict of interest
The authors declare that they have no competing interests.
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