Research Papers:

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

Christina Demuth _, Morten Nørgaard Andersen, Kristine Raaby Jakobsen, Anne Tranberg Madsen and Boe Sandahl Sørensen

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Oncotarget. 2017; 8:68221-68229. https://doi.org/10.18632/oncotarget.19920

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Christina Demuth1, Morten Nørgaard Andersen1, Kristine Raaby Jakobsen1,2, Anne Tranberg Madsen1 and Boe Sandahl Sørensen1

1Department of Clinical Biochemistry, Aarhus University Hospital, DK-8200 Aarhus N, Denmark

2Department of Biomedicine, Aarhus University, DK-8000 Aarhus C, Denmark

Correspondence to:

Christina Demuth, email: [email protected]

Keywords: erlotinib, resistance, NSCLC, PD-L1, MET

Received: June 01, 2017     Accepted: July 25, 2017     Published: August 04, 2017


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.

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PII: 19920