This is a highly relevant point in generalizing the efficacy of anti-PD-1/PD-L1 and anti-CTLA-4 agents across all the stages of HCC, especially given that the majority of patients that have been previously recruited to clinical trials of immune checkpoint inhibitors may have had loco-regional therapies (radiofrequency ablation or TACE). The gene discussed is CTLA4; the disease is hepatocellular carcinoma.