CTLA4 and hepatocellular carcinoma: The first clinical trial data came from the CheckMate 040, the combination of dual PD-1 and CTLA-4 blockades (nivolumab and ipilimumab) achieved an ORR of 31%, and a 24-month OS rate of 40% in advanced HCC who had received sorafenib before, which led to the approval of the combination as 2nd line treatment of HCCs by FDA [137].