TLR9 and hepatocellular carcinoma: R848 has been used as an agonist of TLR7/8 in a variety of tumors and as an immune adjuvant to generate antitumor immune memory.[63, 64] Furthermore, TLR7/8 agonists, rather than TLR3 and TLR9 agonists, can eradicate tumors that evade immune surveillance upon MHC class I downregulation.[65] In this study, we directly addressed three critical issues in HCC using a clinically relevant mouse model.