Inhibition of c-MET upregulates PD-L1 expression in lung adenocarcinoma.
Am J Cancer Res
; 10(2): 564-571, 2020.
Article
em En
| MEDLINE
| ID: mdl-32195027
ABSTRACT
Non-small cell lung cancer (NSCLC) patients with c-MET dysregulation may benefit from c-MET inhibitors therapy as inhibition of c-MET activity has emerged as a therapeutic approach against this disease. Although several c-MET inhibitors have been evaluated in multiple clinical trials in lung cancer, their benefits so far have been modest. Thus, furthering our understanding of the mechanisms contributing to the lack of success of c-MET inhibitors in clinical trials is essential toward the development of rational and effective combination strategies. Here we show that exposure of NCSLC cell lines to c-MET inhibitor tivantinib increases their expression of PD-L1, which in turn causes cells to become more resistant to T-cell killing. Mechanistically, inhibition of c-MET suppresses p-GSK3ß, leading to the stabilization of PD-L1 similar to that observed in liver cancer cells. Collectively, our findings suggest a potential crosstalk between c-MET inhibition and immune escape and provide a rationale for the combination therapy of c-MET inhibitors and immune checkpoint blockade in NSCLC.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Am J Cancer Res
Ano de publicação:
2020
Tipo de documento:
Article