Abstract:

Inhibitory checkpoints, including cytotoxic T lymphocyte?Cassociated antigen 4 (CTLA-4), programmed cell death protein-1(PD-1), and programmed cell death ligand 1 (PD-L1), have been identified to suppress anti-tumor immune responses in solid tumors. The application of immune checkpoint inhibitors (ICIs) have reversed immune exhaustion with promising efficacy in practice, which expanded the spectrum of clinical use. Recent output studies show immune checkpoint therapy provides survival benefit for tremendous numbers of patients with hepatocellular carcinoma(HCC). While with remarkable and durable responses in a subset HCC patients, majority of those will still develop primary non-response or adaptive resistance. The combination treatment strategies with immunotherapy is being evaluated in phase 1, 2 or 3 trials in HCC, and some of the results suggested that an anti-PD-1 antibody combined with other ICIs, Tyrosine Kinase Inhibits（TKI）, systemic therapy or locoregional therapy are more effective treatment strategies. In this review, we summarise recent developments in ICIs-based therapies, and speculate rational deployment of the effective predictive markers and selection of the combination therapy strategies,which should hold promise for improve the efficacy and prognosis of HCC patients.

Key words: hepatocellular carcinoma, immune checkpoint inhibitors, HCC, pembrolizumab, nivolumab, Atezolizumab, targeted therapies