In lung cancer, evaluation of smoking history, tumor mutational burden (TMB), microsatellite instability (MSI), high expression of CTLA4, low expression of CX3CL1 and infiltration of CD8+ T cells within the tumor microenvironment (TME) seems to be superior in predicting therapy responses towards anti-PD-1/PD-L1 directed ICI13–15 when compared to histopathological PD-L1 quantification, however these markers so far could not be translated into a robust and clinically easy to use biomarker signature. This evidence concerns the gene CD274 and lung cancer.