miR-1258 Enhances the Anti-Tumor Effect of Liver Cancer Natural Killer (NK) Cells by Stimulating Toll-Liker Receptor (TLR)7/8 to Promote Natural Killer (NK)-Dendritic Cell (DC) Interaction

Abstract

TLR7/8 agonists are immunomodulators for treating skin cancer or virus infections. miR-1258 can activate TLR7/8. This study aims to explore the role of TLR7/8 agonists and miR-1258 in activating liver cancer NK cells. NK cells and DC cells were treated with TLR7/8 agonists R837, ssRNA40 and miR-1258 followed by analysis of hepatocellular carcinoma (HCC) cell behaviors in vivo and in vitro. TLR7/8 agonist miR-1258 activated NKs and promoted DCs maturation. In addition, DCs also assisted NKs to function and enhance the anti-HCC immune responses. The interaction of DCs with NK cells stimulated by TLR7/8 agonist miR-1258 can significantly inhibit tumor development and metastasis in mice HCC model. TLR7 or TLR8 agonists, especially miR-1258, promoted DCs-NKs interaction by promoting the secretion of related cytokines and cell/cell contact, which increased anti-tumor activity of NKs and promoted DC-NK cells to inhibit the growth of HCC cells. In conclusion, miR-1258 simultaneously stimulates the expression of TLR7/8, and promotes NK-DC cells to inhibit the growth of HCC cells, providing a theoretical basis for the treatment of liver cancer.