In this regard, combination of PD-1/PD-L1 monoclonal antibody and targeting co-stimulatory receptors (such as 4-1BB, OX40, CD27) with agonistic antibodies seems to be a potential therapeutic option for HCC, which may enhance and reverse functions of exhausted CD8+ TILs [179]. This evidence concerns the gene TNFRSF4 and hepatocellular carcinoma.