title: Natural killer cell dysfunction in hepatocellular carcinoma and NK cell-based immunotherapy.
abstract: The mechanisms linking hepatitis B virus (HBV) and hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) remain largely unknown. Natural killer (NK) cells account for 25%-50% of the total number of liver lymphocytes, suggesting that NK cells play an important role in liver immunity. The number of NK cells in the blood and tumor tissues of HCC patients is positively correlated with their survival and prognosis. Furthermore, a group of NK cell-associated genes in HCC tissues is positively associated with the prolonged survival. These facts suggest that NK cells and HCC progression are strongly associated. In this review, we describe the abnormal NK cells and their functional impairment in patients with chronic HBV and HCV infection, which contribute to the progression of HCC. Then, we summarize the association of NK cells with HCC based on the abnormalities in the numbers and phenotypes of blood and liver NK cells in HCC patients. In particular, the exhaustion of NK cells that represents lower cytotoxicity and impaired cytokine production may serve as a predictor for the occurrence of HCC. Finally, we present the current achievements in NK cell immunotherapy conducted in mouse models of liver cancer and in clinical trials, highlighting how chemoimmunotherapy, NK cell transfer, gene therapy, cytokine therapy and mAb therapy improve NK cell function in HCC treatment. It is conceivable that NK cell-based anti-HCC therapeutic strategies alone or in combination with other therapies will be great promise for HCC treatment.
authors.affiliation: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.affiliation: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Hao-yu
authors.initials: HY
authors.lastname: Sun
authors.affiliation: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Wei-hua
authors.initials: WH
authors.lastname: Xiao
authors.affiliation: Institute of Immunopharmacology and Immunotherapy, School of Pharmaceutical Sciences, Shandong University, Ji-nan 250012, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
authors.forename: Zhi-gang
authors.initials: ZG
authors.lastname: Tian
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology; D015316:Genetic Therapy / Q000379:methods; D016174:Hepacivirus / Q000302:isolation & purification; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology* / Q000637:transplantation* / Q000821:virology; D008113:Liver Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy* / Q000821:virology