6533b7d3fe1ef96bd126150c

RESEARCH PRODUCT

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

Alexandros GeorgiouAnna MinchomUdai BanerjiJaishree BhosleTimothy A. YapJohann S. De BonoMary O'brienParames ThavasuAdam StewartZai AhmadSanjay Popat

subject

0301 basic medicineOncologyCell signalingLung NeoplasmsLuminescenceImmunofluorescenceMutantCancer Treatmentlcsh:MedicineSignal transductionERK signaling cascademedicine.disease_causeJurkat cellsB7-H1 AntigenLung and Intrathoracic TumorsMajor Histocompatibility ComplexWhite Blood Cells0302 clinical medicineAnimal CellsCarcinoma Non-Small-Cell LungMedicine and Health Scienceslcsh:ScienceTrametinibMultidisciplinarymedicine.diagnostic_testT CellsChemistryPhysicsElectromagnetic RadiationMEK inhibitorSignaling cascadesOncology030220 oncology & carcinogenesisPhysical SciencesKRASCellular TypesResearch Articlemedicine.medical_specialtyGeneral Science & TechnologyImmune CellsImmunologyResearch and Analysis MethodsImmunofluorescenceFluorescence03 medical and health sciencesCell Line TumorInternal medicineMD MultidisciplinarymedicineHumansImmunoassaysBlood Cellslcsh:RCancers and NeoplasmsBiology and Life SciencesCell BiologyCoculture TechniquesNon-Small Cell Lung Cancerrespiratory tract diseasesGenes ras030104 developmental biologyCell cultureMutationImmunologic TechniquesCancer researchClinical ImmunologyCancer biomarkerslcsh:QClinical Medicine

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 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.

10.1371/journal.pone.0186106http://europepmc.org/articles/PMC5628934?pdf=render