Increased PD-L1 expression in erlotinib-resistant NSCLC cells with MET gene amplification is reversed upon MET-TKI treatment

// Christina Demuth 1 , Morten Norgaard Andersen 1 , Kristine Raaby Jakobsen 1, 2 , Anne Tranberg Madsen 1 and Boe Sandahl Sorensen 1 1 Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200 Aarhus N, Denmark 2 Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark Correspondence to: Christina Demuth, email: Demuth@clin.au.dk Keywords: erlotinib, resistance, NSCLC, PD-L1, MET Received: June 01, 2017      Accepted: July 25, 2017      Published: August 04, 2017 ABSTRACT Introduction: Cancer cells can achieve immune evasion by expressing the programmed death receptor 1 ligand (PD-L1) on the cell surface. Blockade of the receptor (PD-1) can avert this evasion. Here we aim at investigating PD-L1 expression in erlotinib-resistant lung cancer cells with MET proto-oncogene ( MET ) gene amplification. Materials and Methods: We employed an erlotinib-resistant NSCLC cell line with MET gene amplification. PD-L1 mRNA (qPCR) and protein (flow cytometry) expression was investigated after treatment with MET and mitogen-activated protein kinase (MAPK) targeting drugs (crizotinib and SCH772984, respectively). Results: We demonstrate that PD-L1 expression is increased in erlotinib-resistant non-small cell lung cancer (NSCLC) cells with MET gene amplification. Targeted inhibition of MET significantly decreases both gene and protein expression of PD-L1. Further, we demonstrate that inhibiting MAPK also results in a significant decrease in PD-L1 expression. Taken together these results show that expression of PD-L1 in the erlotinib-resistant cell line is associated with MET activity, and the downstream MAPK pathway. Conclusions: Our results demonstrate that PD-L1 expression is increased in erlotinib resistant NSCLC cells with MET gene amplification and that the increase can be averted by targeted inhibition of MET.