Metabolic reprogramming and immune evasion interaction in the tumor microenvironment promote tumor progression.

Emerging evidence demonstrates that tumor metabolic reprogramming not only supports tumor-cell proliferation but also promotes the establishment of an immunosuppressive tumor microenvironment (TME) by altering nutrient competition and metabolite accumulation. Therefore, metabolic reprogramming and immune evasion should be regarded as closely interconnected processes rather than independent phenotypes. By altering the metabolite composition of the TME and local metabolic programs, tumor metabolic reprogramming suppresses immune activation and shapes immune-cell function and fate, thereby promoting cancer immune evasion. This review focuses on two mechanistically developed axes linking tumor metabolism to immune suppression: glycolysis-associated lactate accumulation and lactylation, and nutrient competition involving amino acids and lipids. We summarize how lactate acts as both a metabolic substrate and signaling mediator, how lactylation translates metabolic changes into epigenetic regulation of immune-related transcriptional programs, and how depletion of glutamine, tryptophan, and arginine, together with lipid accumulation and remodeling, impairs effector-cell metabolic fitness while favoring regulatory T cells, tumor-associated macrophages, and myeloid-derived suppressor cells. We further examine hypoxia as a contextual amplifier, the immune-evasion outcomes and reciprocal feedback circuits produced by these alterations, and therapeutic strategies targeting the metabolism-immunity axis. Particular attention is given to context-dependent effects and evidence maturity, because lactate-, hypoxia-, and metabolite-associated pathways are not uniformly immunosuppressive across cell types and conditions. Although preclinical findings support interventions targeting lactate production or transport, lactylation-associated regulators, amino acid metabolism, and the ecto-5'-nucleotidase (CD73)-adenosine axis, clinical evidence remains limited and heterogeneous. Biomarker-guided patient selection, confirmation of target engagement, preservation of immune-cell metabolic fitness, and rational combination strategies will be essential for clinical translation.