microrna-124 enhances t cells functions by manipulating the lactic acid metabolism of tumor cells

High production of lactic acid is a common feature of various tumors. lactic acid is an immunosuppressive molecule with crucial roles in tumor cells' immune escape, which could largely be attributed to its negative effects on the t cells present in the tumor microenvironment (tme). strategies that decrease the glycolysis rate of tumor cells could enhance immunosurveillance and limit tumor growth. pyruvate kinase m2 (pkm2) is a key enzyme in the glycolysis pathway, and it plays a vital role in lactic acid buildup in the tme. microrna (mir)-124 has been shown to be able to decrease tumor cell lactic acid synthesis indirectly by reducing pkm2 levels.in this study, we first overexpressed mir-124 in the tumor cells and evaluated its effects on the pkm2 expression and lactic acid production of the tumor cells using quantitative real-time polymerase chain reaction (qrt-pcr) and spectrophotometry, respectively. then, we cocultured mir-1242013;treated tumor cells with t cells to investigate the effects of mir-124 overexpression on t cell proliferation, cytokine production, and apoptosis.our results demonstrated that mir-124 overexpression could significantly reduce the amount of lactic acid produced by tumor cells by manipulating their glucose metabolism, which led to the augmented proliferation and ifn-3b3; production of t cells. moreover, it rescued t cells from lactic acid-induced apoptosis.our data suggest that lactic acid is a hindering factor for t-cell2013;based immunotherapies; however, manipulating tumor cells' metabolism via mir-124 could be a promising way to improve antitumor responses of t cells.