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A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments.

Authors :
Anna Minchom
Parames Thavasu
Zai Ahmad
Adam Stewart
Alexandros Georgiou
Mary E R O'Brien
Sanjay Popat
Jaishree Bhosle
Timothy A Yap
Johann de Bono
Udai Banerji
Source :
PLoS ONE, Vol 12, Iss 10, p e0186106 (2017)
Publication Year :
2017
Publisher :
Public Library of Science (PLoS), 2017.

Abstract

We investigated PD-L1 changes in response to MEK and AKT inhibitors in KRAS mutant lung adenocarcinoma (adeno-NSCLC). PD-L1 expression was quantified using immunofluorescence and co-culture with a jurkat cell-line transfected with NFAT-luciferase was used to study if changes in PD-L1 expression in cancer cell lines were functionally relevant. Five KRAS mutant cell lines with high PD-L1 expression (H441, H2291, H23, H2030 and A549) were exposed to GI50 inhibitor concentrations of a MEK inhibitor (trametinib) and an AKT inhibitor (AZD5363) for 3 weeks. Only 3/5 (H23, H2030 and A549) and 2/5 cell lines (H441 and H23) showed functionally significant increases in PD-L1 expression when exposed to trametinib or AZD5363 respectively. PD-L1 overexpression is not consistent and is unlikely to be an early mechanism of resistance to KRAS mutant adeno-NSCLC treated with MEK or AKT inhibitors.

Subjects

Subjects :
Medicine
Science

Details

Language :
English
ISSN :
19326203
Volume :
12
Issue :
10
Database :
Directory of Open Access Journals
Journal :
PLoS ONE
Publication Type :
Academic Journal
Accession number :
edsdoj.4ba8300624ba49feb4e4b6abd7128670
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pone.0186106