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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
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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. |
format | Online Article Text |
id | pubmed-5628934 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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