Despite the fact that TLR9 agonists alone were unable to elicit significant systemic antitumor immune responses due to their immunosuppressive effects when combined with an anti-PD-1 antibody or anti-PD-L1, they yielded an additive effect via negative regulation of PARP1/STAT3 in a clinical trial in hepatocellular carcinoma [64]. This evidence concerns the gene STAT3 and hepatocellular carcinoma.