Nutritional biomarkers regulating tumor immune microenvironment in osteosarcoma and as predictors of immune checkpoint inhibitor responses.

Osteosarcoma(OS) exhibits poor and heterogeneous responses to immune checkpoint inhibitors(ICIs), largely due to its highly tumor immunosuppressive microenvironment(TIME). This review explores how nutritional biomarkers regulate the OS tumor microenvironment(TME) and serve as predictors of ICIs efficacy. Key biomarkers, including prognostic nutritional index(PNI), vitamin D and IDO modulate tumor-infiltrating lymphocytes (TILs), CD8+ T-cell function, macrophage polarization, and cytokine-metabolite crosstalk through mechanisms such as nutrient depletion, lactate acidification, and inflammatory signaling. These biomarkers not only reflect host nutritional and inflammatory status but also actively shape an TIME that contributes to ICIs resistance. Targeted nutritional interventions and combinations with IDO show potential to reprogram the TME and enhance antitumor immunity. This review highlights the value of nutritional biomarkers for patient stratification, prognostic assessment, and the development of personalized nutrition-immunotherapy strategies, providing a foundation for overcoming treatment resistance in OS.