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Peer-reviewedCC BY 4.0Frontiers in Immunology

Advancing osteosarcoma treatment: the impact of intratumoral metabolic reprogramming on immunotherapy

  • Jiawei Yin1
  • Shuai Lu2,3
  • Yikai Liu1
  • Maoqi Gong2
  • Yejun Zha2
  • Xieyuan Jiang2,3
  1. 1Beijing Jishuitan Hospital, Capital Medical University
  2. 2Department of Orthopedic Trauma, Beijing Jishuitan Hospital, Capital Medical University
  3. 3Beijing Research Institute of Traumatology and Orthopaedics
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Abstract

Osteosarcoma (OS) remains difficult to cure once it becomes metastatic, recurrent, or resistant to chemotherapy, and immune checkpoint blockade has provided limited clinical benefit. The metabolic-immune tumor microenvironment (TME) is one barrier to effective immunity because malignant, stromal, and immune cells compete for nutrients and adapt to hypoxia, acidosis, and matrix-related constraints. This review examines how cancer-associated fibroblasts, extracellular matrix, myeloid and lymphoid populations interact with glucose/lactate, glutamine, arginine, and lipid metabolism in OS. Public OS single-cell RNA sequencing datasets are used to illustrate cellular heterogeneity and are interpreted alongside published experimental evidence. OS-specific evidence is most developed for glycolysis and acidosis, glutamine dependence, myeloid regulation, and selected stromal and lipid-related pathways. Arginine-directed approaches, NK-cell immunometabolism, and most metabolism-ICB combinations remain preclinical or are supported mainly by mechanistic evidence from other tumor types. Together, these findings highlight the mechanisms with the strongest current support and the major gaps that remain before clinical translation.

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Cite

BibTeXRIS
BibTeX
@article{yin2026advancing,
  title = {{Advancing osteosarcoma treatment: the impact of intratumoral metabolic reprogramming on immunotherapy}},
  author = {Jiawei Yin and Shuai Lu and Yikai Liu and Maoqi Gong and Yejun Zha and Xieyuan Jiang},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1928701},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1928701/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Advancing osteosarcoma treatment: the impact of intratumoral metabolic reprogramming on immunotherapy
AU  - Jiawei Yin
AU  - Shuai Lu
AU  - Yikai Liu
AU  - Maoqi Gong
AU  - Yejun Zha
AU  - Xieyuan Jiang
PY  - 2026
DA  - 2026/10/07
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1928701
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1928701/full
AB  - Osteosarcoma (OS) remains difficult to cure once it becomes metastatic, recurrent, or resistant to chemotherapy, and immune checkpoint blockade has provided limited clinical benefit. The metabolic-immune tumor microenvironment (TME) is one barrier to effective immunity because malignant, stromal, and immune cells compete for nutrients and adapt to hypoxia, acidosis, and matrix-related constraints. This review examines how cancer-associated fibroblasts, extracellular matrix, myeloid and lymphoid populations interact with glucose/lactate, glutamine, arginine, and lipid metabolism in OS. Public OS single-cell RNA sequencing datasets are used to illustrate cellular heterogeneity and are interpreted alongside published experimental evidence. OS-specific evidence is most developed for glycolysis and acidosis, glutamine dependence, myeloid regulation, and selected stromal and lipid-related pathways. Arginine-directed approaches, NK-cell immunometabolism, and most metabolism-ICB combinations remain preclinical or are supported mainly by mechanistic evidence from other tumor types. Together, these findings highlight the mechanisms with the strongest current support and the major gaps that remain before clinical translation.
SN  - 1664-3224
ER  -