Regulation Of PD-L1 Expression By Lactate In Lung Adenocarcinoma Cell Lines

Objective:This project aimed to investigate the relationship between the expression of PD-L1 and lactate in lung adenocarcinoma cell lines and its possible mechanism.Methods: Human lung adenocarcinoma cell lines A549,H1299 and Jurkat T cells were selected as the research object.(1)Western and QPCR were used to investigate the correlation between lactate and the expression of TAZ and PD-L1.(2)Western blot and ELISA were used to investigate the correlation between c AMP/PKA signaling pathway,and the regulation of PD-L1 expression by lactate/GPR81.(3)Transfection plasmid and si RNA were used to investigate the mechanism of PD-L1 mediated by Hippo signal transduction pathway.(4)ELISA and flow cytometry were used to analyze the relationship between the lactate in the tumor microenvironment and immune escape.Results: 1.Lactate promotes PD-L1 expression through its receptor GPR81,in lung adenocarcinoma cell line.1.Lactate /GPR81 regulates PD-L1 expression by inhibiting c AMP/PKA.2.Hippo/TAZ mediated regulation of lactate on PD-L1.4.Rho A and LATS1 mediate the regulation of PD-L1 by lactate /GPR81.5.TAZ-TEAD1 complex mediated lactate induced PD-L1 expression.6.The high expression of PD-L1 induced by lactic acid can inhibit the immune response.Conclusion:1.Hippo-TAZ signaling pathway mediates the regulation of PD-L1 by lactate /GPR81.2.Lactate is likely to affect the PD-1/PD-L1 pathway to inhibit the function of T cells in tumor microenvironment to promote the immune escape of tumor cells.