In this study, we analyzed the changes in soluble immune checkpoints and different circulating T cell subsets belonging to the activatory (PD1+ and CD137+), proliferating (Ki67+) and inhibitory (Tregs, PMN(Lox1+)- and M-MDSCs) immune subsets in advanced non-oncogene addicted NSCLC patients before and after the first cycle of ICIs to highlight the relevance of continuously monitoring the immune fitness of cancer patients for the optimization of the therapeutic choice. This evidence concerns the gene TNFRSF9 and cancer.