Work

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

Year: 2026

Type: review

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.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1928701

Authors: Jiawei Yin, Shuai Lu, Yikai Liu, Maoqi Gong, Yejun Zha, Xieyuan Jiang

Institutions: Capital Medical University, Beijing Jishuitan Hospital

Language: English

Topic: Sarcoma Diagnosis and Treatment

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801