Clinical trials are currently ongoing to evaluate the utility of antibodies 
against programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), 
and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) as monotherapy or 
combination therapy in patients with hepatocellular carcinoma (HCC). Results of 
combination treatment with the anti-PD-L1 antibody durvalumab and the 
anti-CTLA-4 antibody tremelimumab in HCC were presented at the 2017 annual 
meeting of the ASCO (American Society of Clinical Oncology). Response rates were 
25% in all 40 patients and 40% in the 20 uninfected patients, both of which are 
encouraging. Transcatheter arterial chemoembolization and radiofrequency 
ablation can activate tumor immunogenicity by releasing tumor-associated antigen 
and by inducing the migration of cytotoxic T lymphocytes to small intrahepatic 
metastatic nodules. Subsequent administration of anti-PD-1 antibody could 
control these small intrahepatic metastatic nodules. In a nonclinical study, the 
combination of pembrolizumab and lenvatinib inhibited the cancer 
immunosuppressive environments induced by tumor-associated macrophages and 
regulatory T cells. This, in turn, decreased the levels of TGF-β and IL-10, the 
expression of PD-1, and the inhibition of Tim-3, triggering anticancer immunity 
mediated by immunostimulatory cytokines such as IL-12. Studies such as these may 
provide insight into the appropriate molecular targeted agents to be used with 
immune checkpoint inhibitors.