PLoS ONE (Jan 2017)

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

  • 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

DOI
https://doi.org/10.1371/journal.pone.0186106
Journal volume & issue
Vol. 12, no. 10
p. e0186106

Abstract

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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.