After conducting a retrospective analysis of 110 NSCLC samples using the clinically recommended immune checkpoint biomarkers of PD-L1 and TMB by targeted next generation sequencing, we identified a substantial subpopulation of PD-L1-, TMB- patients (24%; n = 26) of which 46% presented an inflamed TME as measured by TIGS. This evidence concerns the gene CD274 and non-small cell lung carcinoma.