Compared to non-viral HCC, the Tregs detected in HBV-HCC uniquely expressed PD-1, which exhausted functional CD8+ T- cells (as marked by low granzyme A/B and perforin and blunted proliferation) within the tumor microenvironment [155,167], explaining the reduced sensitivity of the non-viral HCC to PD1 treatment [168]. The gene discussed is PRF1; the disease is hepatocellular carcinoma.