Hepatocellular carcinoma (HCC) is at the focus of intense research efforts for the development of immune checkpoint inhibitors (ICI).1 Targeted inhibition of programmed cell death (PD-1) receptor/ligand (PD-1/PD-L1) interaction results in measurable anti-tumor responses in a fraction of patients with advanced HCC, a finding that led to the breakthrough approval of nivolumab2 and pembrolizumab3 by the Food and Drug Administration in light of the results of small, single-arm open-label studies. This evidence concerns the gene CD274 and hepatocellular carcinoma.