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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

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 c...

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Autores principales: Minchom, Anna, Thavasu, Parames, Ahmad, Zai, Stewart, Adam, Georgiou, Alexandros, O’Brien, Mary E. R., Popat, Sanjay, Bhosle, Jaishree, Yap, Timothy A., de Bono, Johann, Banerji, Udai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628934/
https://www.ncbi.nlm.nih.gov/pubmed/28982179
http://dx.doi.org/10.1371/journal.pone.0186106
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author Minchom, Anna
Thavasu, Parames
Ahmad, Zai
Stewart, Adam
Georgiou, Alexandros
O’Brien, Mary E. R.
Popat, Sanjay
Bhosle, Jaishree
Yap, Timothy A.
de Bono, Johann
Banerji, Udai
author_facet Minchom, Anna
Thavasu, Parames
Ahmad, Zai
Stewart, Adam
Georgiou, Alexandros
O’Brien, Mary E. R.
Popat, Sanjay
Bhosle, Jaishree
Yap, Timothy A.
de Bono, Johann
Banerji, Udai
author_sort Minchom, Anna
collection PubMed
description 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 GI(50) 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.
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spelling pubmed-56289342017-10-20 A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments Minchom, Anna Thavasu, Parames Ahmad, Zai Stewart, Adam Georgiou, Alexandros O’Brien, Mary E. R. Popat, Sanjay Bhosle, Jaishree Yap, Timothy A. de Bono, Johann Banerji, Udai PLoS One Research Article 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 GI(50) 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. Public Library of Science 2017-10-05 /pmc/articles/PMC5628934/ /pubmed/28982179 http://dx.doi.org/10.1371/journal.pone.0186106 Text en © 2017 Minchom et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Minchom, Anna
Thavasu, Parames
Ahmad, Zai
Stewart, Adam
Georgiou, Alexandros
O’Brien, Mary E. R.
Popat, Sanjay
Bhosle, Jaishree
Yap, Timothy A.
de Bono, Johann
Banerji, Udai
A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments
title A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments
title_full A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments
title_fullStr A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments
title_full_unstemmed A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments
title_short A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments
title_sort study of pd-l1 expression in kras mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628934/
https://www.ncbi.nlm.nih.gov/pubmed/28982179
http://dx.doi.org/10.1371/journal.pone.0186106
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