摘 要：乳酸长期被视为糖酵解的代谢副产物。近年来研究发现，其在肿瘤免疫微环境（TIME）中具有关键调控作用。乳酸积累通过干扰代谢平衡、抑制T细胞和NK细胞功能、诱导免疫抑制性细胞极化，重塑TIME的免疫景观。与此同时，乳酸化作为新型蛋白质翻译后修饰，介导代谢信号对表观遗传调控事件的调控，促进免疫相关基因（如PD-L1、IL-10、Arg1）的表达，进一步增强免疫逃逸。本文聚焦乳酸及乳酸化修饰在TIME中的代谢-表观遗传协同机制，阐述乳酸的产生与穿梭、免疫细胞代谢互作及乳酸稳态失衡的临床诊疗潜力，深入理解乳酸-乳酸化轴的免疫调控机制，为肿瘤免疫治疗提供新的分子靶点与研究方向。
关键词：乳酸；乳酸化；肿瘤代谢；免疫调控；治疗耐药
中图分类号：R730.23             文献标志码：A                  DOI：10.3969/j.issn.1007-7146.2025.06.005

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）