Molecular mechanisms and clinical significance of the glioma metabolic-immune axis: a comprehensive review

Glioma is the most common and highly aggressive tumor of the central nervous system. Increasing evidence indicates that metabolic reprogramming and the tumor immune microenvironment are intricately interconnected and jointly contribute to tumor initiation, progression, and therapeutic resistance. In recent years, advances in multi-omics technologies have revealed that multiple metabolic pathways-including nucleotide, amino acid, and lipid metabolism-are closely associated with immune cell infiltration, immune evasion, and clinical outcomes in glioma, leading to the emergence of the "metabolic-immune axis" concept. This review systematically summarizes the regulatory mechanisms by which metabolic reprogramming shapes the glioma immune microenvironment and highlights key metabolic genes and immune phenotypes as potential molecular biomarkers for prognosis prediction and immunotherapeutic response. We further discuss multi-omics-based glioma classification strategies, the mechanistic roles of metabolic pathways in immune escape, and the therapeutic potential of combining metabolic-targeted interventions with immunotherapy. By integrating current research advances and existing challenges, this review aims to provide a comprehensive framework for understanding the metabolic-immune interplay in glioma and to identify promising targets for precision therapy and future clinical translation.