Role of MAPK activity in PD-L1 expression in hepatocellular carcinoma cells.

Abstract

PURPOSE: This study was set out to explore the role of MAPK activity in programmed cell death ligand-1 (PD-L1) expression in hepatocellular carcinoma (HCC) cells. METHODS: The protein expression of PD-L1 was determined by immunofluorescence and immunohistochemistry, and the expression levels of PD-L1 and MAPK-related proteins were determined by flow cytometry and Western blotting. Meanwhile, the RNA transcription level of CD274 was determined by qRT-PCR. RESULTS: Interferon-γ (IFN-γ), epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase (MAPK) signaling pathways were associated with CD274 gene expression in HCC. Epidermal growth factor (EGF) or IFN-γ stimulation increased CD274 mRNA and PD-L1 protein levels in a representative HCC cell line group, further enhanced by EGF and IFN-γ stimulation. Inhibition of the MAPK pathway by EGFR inhibitors ositinib or MEK 1 and 2 inhibitors selumetinib prevented the up-regulation of CD274 mRNA and PD-L1 proteins and membranes induced by EGF and IFN-γ. IFN-γ increased the transcriptional activity of CD274, while MAPK signaling enhanced the stability of CD274 mRNA. CONCLUSION: MAPK pathway activity plays a key role in PD-L1 expression in EGF and IFNγ-induced HCC and may provide a target for improving the efficacy of immunotherapy.