title: TLR7/8 agonists promote NK-DC cross-talk to enhance NK cell anti-tumor effects in hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a common cancer worldwide and the third leading cause of cancer death. Immunotherapy is considered a promising treatment with the aim to boost or arouse HCC-specific immune responses. TLR7 and TLR8 agonists are effective immunomodulators and have been applied topically for the treatment of certain skin tumors and viral infections. Here, we explored the role of TLR7 and TLR8 agonists on the activation of dendritic cells (DCs) and natural killer (NK) cells. We demonstrated that these agonists could directly activate NK cells, promoting the maturation of immature DCs. Meanwhile, DCs also assisted in the function of NK cells, resulting in enhanced anti-tumor immune responses to HCC. Importantly, the combination therapy with NK cells stimulated with DCs and TLR7/8 agonist Gardiquimod (GDQ) significantly suppresses the growth of human HepG2 liver carcinoma xenografts. This study provides a new immunotherapeutic approach for human HCC based on DC-NK cross-talk and also suggests that TLR7 and/or TLR8 agonists, particularly GDQ, may serve as potent innate and adaptive immune response immunomodulators in tumor therapy.
authors.affiliation: Institute of Immunopharmacology & Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, China.
authors.forename: Zhixia
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Institute of Immunopharmacology & Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Institute of Immunopharmacology & Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, Anhui, China. Electronic address: tzg@ustc.edu.cn.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Institute of Immunopharmacology & Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, Shandong, China. Electronic address: caizhangsd@sdu.edu.cn.
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D007694:Killer Cells, Natural / Q000276:immunology*; D008113:Liver Neoplasms / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051199:Toll-Like Receptor 7 / Q000276:immunology* / Q000378:metabolism; D051200:Toll-Like Receptor 8 / Q000276:immunology* / Q000378:metabolism
chemical_list: D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8
keywords: Cross-talk; DC; Hepatocellular carcinoma (HCC); NK cell; TLR7/8 agonist