Since the pilot phase II trial of the CTLA-4 blockade tremelimumab as a single agent in 21 patients with advanced HCV-associated HCC with an objective response rate (ORR) of 17.6% [113], PD-1 antibodies, nivolumab and pembrolizumab had been approved by U.S. Food and Drug Administration (FDA) as the 2nd line treatment for advanced HCC based on the results of the CheckMate 040 and KEYNOTE-224 trials, in which nivolumab and pembrolizumab produced an ORR of 15–20% including 1–5% complete response (CR), and prolonged survivals [114, 115]. Here, CTLA4 is linked to hepatocellular carcinoma.