Dong Zening, Yuan Zhangchen, Jin Tianqiang, Gao Chao, Wang Xiaoyu, Xu Feng
Hepatobiliary and Splenic Surgery Ward, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
Zhongshan Hospital, Liver Cancer Institute, Key Laboratory of Carcinogenesis and Cancer Invasion, Department of Liver Surgery, Ministry of Education, Fudan University, Shanghai, China.
J Transl Med. 2025 Nov 7;23(1):1239. doi: 10.1186/s12967-025-07272-x.
Lactate, initially considered a mere metabolic byproduct, has emerged as a pivotal metabolite in the tumor microenvironment (TME), playing critical roles across a range of pathological conditions. In tumors in particular, lactate contributes to disease progression through its multifaceted biological functions. Recent studies have further identified lactate as a central mediator in the regulation of tumor immune evasion. Tumor cells, via aerobic glycolysis, secrete large amounts of lactate, leading to acidification of the TME and suppression of antitumor immunity through various mechanisms, including immune cell inhibition, epigenetic reprogramming, and metabolic competition. These findings have fueled growing interest in targeting lactate as a therapeutic strategy against cancer, encompassing approaches such as LDHA inhibitors, MCT inhibitors, and novel nanomedicine-based therapies. In this review, we summarize lactate metabolism in the body, explore its impact on various immune cell populations, elucidate its functional roles in tumor biology, and highlight recent advances in antitumor strategies that target lactate.
