Increased Lactate in Gastric Cancer Tumor-Infiltrating Lymphocytes Is Related to Impaired T Cell Function Due to miR-34a Deregulated Lactate Dehydrogenase A

Cellular Physiology and Biochemistry

Wang Ping¹ 

关键词: Lactate;    Lactate dehydrogenase A;    miR-34a;    Th1 cells;    Cytotoxic T lymphocytes;   

DOI  :  10.1159/000493110

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims Lactate is one of the products of glycolysis and is a hallmark of the Warburg effect. Glycolysis is found in tumor as well as immune cells. However, the effects of lactate on the function of tumor-infiltrating T cells (TILs) are rarely reported. Methods In the present study, we investigated lactate and other glycolysis-related metabolites within TILs of human gastric cancer (GC). Lactate concentration was determined by liquid chromatography–mass spectrometry. The functional effects and clinical relevance of excessive lactate on T cells were investigated in clinical samples, and the mechanism of increased lactate was explored. Results Lactate was significantly increased in GC TILs and related to decreased T helper (Th)1 cells and cytotoxic T lymphocytes (CTLs). Increased lactate within GC TILs was positively correlated with increased lactate dehydrogenase A (LDH)A. Expression of LDHA in GC TILs was also negatively correlated with percentages of Th1 cells and CTLs. Decreased miR-34a expression in GC TILs was responsible for increased expression of LDHA. A hypoxic tumor environment was responsible for decreased miR-34a and lactate-induced impaired immune function. Conclusion We found that hypoxia decreases miR-34a expression and lose miR-34a regulation on LDHA, thus increasing lactate level within GC TILs and impairing immune function in GC.

【 授权许可】

CC BY-NC-ND