Based on our findings, we suggest: (1) it is important to consider a patient’s smoking status before embarking on anti-PD-1/PD-L1/UTLA-4/MUC1 treatment of NSCLC; (2) smoking status may be considered as a clinical predictor for the treatment of urothelial carcinoma, and head and neck cancer by PD-1/PD-L1 inhibitors. This evidence concerns the gene CD274 and head and neck cancer.