A study of PD-L1 expression in KRAS mutant non-small cell lung cancer cell lines exposed to relevant targeted treatments.
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Date
2017-10-05Author
Minchom, A
Thavasu, P
Ahmad, Z
Stewart, A
Georgiou, A
O'Brien, MER
Popat, S
Bhosle, J
Yap, TA
de Bono, J
Banerji, U
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
Cell Line, Tumor
Humans
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Coculture Techniques
Mutation
Genes, ras
B7-H1 Antigen
Research team
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Prostate Cancer Targeted Therapy Group
Thoracic Oncology
Treatment of thoracic tumours
Language
eng
Date accepted
2017-09-25
License start date
2017-01
Citation
PloS one, 2017, 12 (10), pp. e0186106 - ?
Publisher
PUBLIC LIBRARY SCIENCE