The landmark Checkmate 040 trial led to the Food and Drug Administration (FDA) approval for the use of the immune checkpoint inhibitors (ICIs) nivolumab (directed against programmed death-1, or PD-1) plus ipilimumab (directed against cytotoxic T-lymphocyte-associated-protein 4, or CTLA-4) for the treatment of advanced HCC previously treated with sorafenib [15]. The gene discussed is CTLA4; the disease is hepatocellular carcinoma.