Gao Chunyan, Li Jiali, Shan Baoen
Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, China; Key Laboratory of Tumor Prevention, Precision Diagnosis and Treatment of Hebei, Clinical Oncology Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, China.
Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, China; Key Laboratory of Tumor Prevention, Precision Diagnosis and Treatment of Hebei, Clinical Oncology Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050017, China.
Biochim Biophys Acta Rev Cancer. 2025 Jul;1880(3):189339. doi: 10.1016/j.bbcan.2025.189339. Epub 2025 Apr 29.
The tumor microenvironment (TME) arises from the dynamic interactions between tumor cells and the surrounding medium, including a variety of cell types and extracellular components, which have an important impact on the genesis and development of tumors. A key player in TME is lactate, a metabolic byproduct of glycolysis, which serves as a significant energy source. Lactate has direct implications on the survival and differentiation of immune cells, the metabolic reprogramming and progression of tumor cells. Moreover, lactylation, a unique post-translational modification, exerts a regulatory effect on TME by affecting gene transcription via adding lactate groups to both histone and non-histone proteins. This review systematically and comprehensively synthesizes emerging evidence on how the lactate-lactylation axis drives immune evasion, therapy resistance, and TME remodeling, highlighting the therapeutic targets related to lactate and lactylation that dismantle this metabolic-epigenetic crosstalk.
肿瘤微环境（TME）源于肿瘤细胞与周围介质之间的动态相互作用，周围介质包括多种细胞类型和细胞外成分，它们对肿瘤的发生和发展具有重要影响。TME中的一个关键因素是乳酸，它是糖酵解的代谢副产物，可作为重要的能量来源。乳酸对免疫细胞的存活和分化、肿瘤细胞的代谢重编程和进展具有直接影响。此外，乳酰化是一种独特的翻译后修饰，通过向组蛋白和非组蛋白添加乳酸基团来影响基因转录，从而对TME发挥调节作用。本综述系统全面地综合了关于乳酸-乳酰化轴如何驱动免疫逃逸、治疗抗性和TME重塑的新证据，强调了与乳酸和乳酰化相关的治疗靶点，这些靶点可消除这种代谢-表观遗传的相互作用。
