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.
Highlights
Lung cancer is the leading cause of cancer death in developed countries with 1.8 million new lung cancer diagnoses occurring globally per annum [1]
H441, H2291, H2030, H23 and A549 cell lines were chosen for further experiments of AKT and MEK inhibitor exposure as they showed the highest expression of PD-L1 and baseline expression was reproducibly detectable
The five chosen cell lines were exposed to trametinib or AZD5363 at GI50 dose for 3 weeks and the PD-L1 expression quantified by immunofluorescence and expressed in comparison to control (Fig 2 and Table 1)
Summary
Lung cancer is the leading cause of cancer death in developed countries with 1.8 million new lung cancer diagnoses occurring globally per annum [1]. Standard of care options for metastatic NSCLC have evolved from chemotherapy doublets to targeted treatments such as EGFR and ALK inhibitors in defined subsets of patients [2] [3] [4] [5] and, most recently, immune checkpoint modulating drugs [6] [7]. PD-1 inhibitors have shown benefit in the first and second-line setting in both squamous and adenocarcinoma of the lung (adeno-NSCLC) [7] [9] [10]. KRAS mutations are found in 33% of advanced adeno-NSCLC [11]. There are currently no drugs in clinical evaluation that directly inhibit KRAS.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
