The cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and the programmed cell death protein-1 (PD-1) and its ligand (PD-L1) axis were the first immune checkpoints to be targeted with specific inhibitors (ICIs), which are now available in the clinical practice for the treatment of several tumors, including non-small cell lung cancer (NSCLC). The gene discussed is CD274; the disease is non-small cell lung carcinoma.