CTLA4 and hepatocellular carcinoma: CD8+ T cells, which are the main effectors of anti-tumor adaptive immune responses, upregulate immune checkpoint molecules such as PD-1, in addition to CTLA-4, hepatitis A virus cellular receptor 2 (TIM-3), and lymphocyte activating gene 3 (LAG-3) in patients with HCC, and blocking them in vitro significantly restored the function of exhausted CD8+ T cells [21,22].