Over the past decade, immunotherapies have transformed cancer treatment, with immune checkpoint blockade (ICBs) against programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) axes emerging as the frontline therapy for metastatic melanoma. The gene discussed is CD274; the disease is cancer.