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 : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Wang PingLu Long

Abstract

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. 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. 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. We found that hypoxia decreases miR-34a expression and lose miR-34a regulation on L...Continue Reading

Citations

Nov 12, 2019·Frontiers in Molecular Biosciences·Haydn Munford, Sarah Dimeloe
Apr 18, 2020·Frontiers in Oncology·Matthias LäscheCarsten Gründker
Aug 30, 2020·Journal of Experimental & Clinical Cancer Research : CR·Xiang LiQiang You
Aug 9, 2020·Life Sciences·Forough TaheriSomayeh Reiisi
Mar 26, 2021·Frontiers in Cell and Developmental Biology·Wen Jess LiDean G Tang
Dec 1, 2020·Molecular Therapy Oncolytics·Hamed Mirzaei, Michael R Hamblin
Jun 24, 2021·Journal of Gastroenterology and Hepatology·Xiaoling GaoChaojun Wei
Oct 5, 2021·Human Cell·Xingchen WangXiuzhen Han

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