CTLA4 and hepatocellular carcinoma: The CheckMate-040 study demonstrated that the combination of the PD-1 antibody nivolumab and the CTLA-4 inhibitor ipilimumab as a second-line treatment for HCC achieved an ORR of 32%, with a median OS of 22.8 months, significantly prolonging survival, prompting FDA approval for second-line treatment of HCC (Yau et al., 2020).