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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ICR Authors
Authors
Minchom, A
Thavasu, P
Ahmad, Z
Stewart, A
Georgiou, A
O'Brien, MER
Popat, S
Bhosle, J
Yap, TA
de Bono, J
Banerji, U
Thavasu, P
Ahmad, Z
Stewart, A
Georgiou, A
O'Brien, MER
Popat, S
Bhosle, J
Yap, TA
de Bono, J
Banerji, U
Document Type
Journal Article
Date
2017-10-05
Date Accepted
2017-09-25
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.
Citation
PloS one, 2017, 12 (10), pp. e0186106 - ?
Source Title
Publisher
PUBLIC LIBRARY SCIENCE
ISSN
1932-6203
eISSN
1932-6203
Collections
Research Team
Clinical Pharmacology – Adaptive Therapy
Medicine Drug Development Unit (de Bono)
Prostate Cancer Targeted Therapy Group
Thoracic Oncology
Treatment of thoracic tumours
Medicine Drug Development Unit (de Bono)
Prostate Cancer Targeted Therapy Group
Thoracic Oncology
Treatment of thoracic tumours