Stutvoet TS, et al. - By using RNA sequencing data from The Cancer Genome Atlas (TCGA) lung adenocarcinoma and squamous cell lung carcinoma datasets, researchers identified pathways regulating CD274 [programmed death-ligand 1 (PD-L1)] expression in this non-small cell lung cancer (NSCLC) subtype. Using validated signatures for RAS or MEK activation, activation of the MAPK pathway was determined. Findings suggested that MAPK pathway activity plays a key role in the expression of PD-L1 induced by EGF and IFNγ in lung adenocarcinoma without targeted genetic alterations and may be a target for improving the effectiveness of immunotherapy. In this lung cancer subtype, this provides a rationale to explore the combination of MAPK pathway inhibitors with immunotherapy.