title: Combinatorial immunotherapy of sorafenib and blockade of programmed death-ligand 1 induces effective natural killer cell responses against hepatocellular carcinoma.
abstract: Sorafenib, a multi-tyrosine kinase inhibitor, is a standard treatment for advanced hepatocellular carcinoma (HCC). Herein, we report that the combinatorial therapy of sorafenib and anti-programmed death-ligand 1 (PD-L1) monoclonal antibody (mAb) can be implemented with good results for HCC. Cancer mouse models were used to evaluate therapeutic efficacy and examine the immunologic mechanisms of the sorafenib/anti-PD-L1 mAb therapy. The combined administration of sorafenib and anti-PD-L1 mAb into tumor-bearing mice generated potent immune responses resulting in the complete eradication or remarkable reduction of tumor growth. In some instances, the sorafenib/anti-PD-L1 mAb therapy induced long-lasting protection against tumor rechallenges. The results indicate that NK cells but not CD4T cells or CD8 cells mediated the therapeutic efficacy of this combinatorial therapy. The overall results suggest that immunotherapy consisting of the combination of sorafenib/anti-PD-L1 mAb could be a promising new approach for treating patients with HCC.
authors.affiliation: Department of Infectious Disease, The Fourth Affiliated Hospital of Harbin Medical University, Yiyuan Street, Nangang District, Harbin, 150001, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
authors.forename: Hongxia
authors.initials: H
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Liang
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Xiaqi
authors.initials: X
authors.lastname: Mei
authors.forename: Yingji
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D060890:B7-H1 Antigen / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D012189:Retrospective Studies; D000077157:Sorafenib
chemical_list: D000911:Antibodies, Monoclonal; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib