Abstract: Lactate has long been regarded as a metabolic byproduct of glycolysis. Recent studies, however, have revealed its pivotal role in regulating the tumor immune microenvironment (TIME). Excess lactate accumulation disrupts metabolic balance, suppresses the activity of T cells and NK cells, and induces the polarization of immunosuppressive cells, thereby reshaping the immune landscape of TIME. Meanwhile, lactylation, as a novel post-translational protein modification, mediates the regulation of epigenetic events by metabolic signals, promoting the expression of immune-related genes, such as PD-L1, IL-10, and Arg1, and further enhancing immune evasion. This review focuses on the metabolic-epigenetic coordination of lactate and lactylation in TIME, elaborating on lactate production and shuttling, immune-cell metabolic interactions, and the clinical potential of targeting lactate homeostasis. A deeper understanding of the lactate-lactylation axis may provide novel molecular targets and research directions for future tumor immunotherapy.
Key words: lactate; lactylation; tumor metabolism; immune regulation; therapeutic resistance
（Acta Laser Biology Sinica, 2025, 34(6): 515-522）