KRAS mutants to regulate PD-L1 expression through NF-ƘB and HIF-1α pathways in non-small cell lung cancer cells.

e20049Background: PD-L1 (programmed death ligand 1) is expressed in various kinds of human tumors including non-small cell lung cancer (NSCLC) and is of critical importance for the immune escape of tumor cells by inhibiting T cell function via its coinhibitory receptor, programmed death 1 (PD-1). Some driver gene mutations including KRAS have been reported to be involved in intrinsic regulation of PD-L1 expression. However, the potential role and precise mechanism of KRAS mutants in regulation of PD-L1 expression in NSCLC cells remain obscure. Methods: We first examined the expression of PD-L1 and key molecules of KRAS signaling pathway in a panel of NSCLC cells with wild-type or mutant KRAS gene. Additionally, KRAS mutant transfection and pharmacological inhibitors of MEK/ERK, PI3K/AKT, and NF-κB were employed to elucidate the regulation mechanism of PD-L1 expression by KRAS mutant in NSCLC cells. We further analyzed KRAS status and protein levels of PD-L1 and hypoxia inducible factor 1 alpha (HIF-1α) in...