Oncotarget

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

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

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

Metrics: PDF 1019 views  |   HTML 1477 views  |   ?  


Abstract

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: 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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 19920