title: Functional impairment in circulating and intrahepatic NK cells and relative mechanism in hepatocellular carcinoma patients.
abstract: Functional defects in natural killer (NK) cells have been proposed to be responsible for the failure of anti-tumor immune responses. Whether and how NK cells are impaired in hepatocellular carcinoma (HCC) patients remain unknown. In this study, we found that HCC patients displayed a dramatic reduction in peripheral CD56(dim)CD16(pos) NK subsets compared with healthy subjects. A significant reduction of CD56(dim)CD16(pos) NK subsets was also found in tumor regions compared with non-tumor regions in the livers of these HCC patients. Both these peripheral and tumor-infiltrating NK cells exhibited poorer capacity to produce IFN-gamma and kill K562 targets, which was further found to be associated with increased CD4(+)CD25(+) T regulatory cells as we previously-described in HCC patients. Addition of Tregs from HCC patients efficiently inhibited the anti-tumor ability of autologous NK cells in vitro. These findings are helpful for understanding the mechanism of NK cell-mediated anti-tumor immune responses in HCC patients.
authors.affiliation: Institute of Microbiology, Chinese Academy of Sciences, Beijing 100012, China.
authors.forename: Lun
authors.initials: L
authors.lastname: Cai
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.forename: Junliang
authors.initials: J
authors.lastname: Fu
authors.forename: Shuye
authors.initials: S
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yang
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.forename: Po
authors.initials: P
authors.lastname: Tien
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D019002:CD56 Antigen / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000276:immunology*; D016022:Case-Control Studies; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008113:Liver Neoplasms / Q000097:blood / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017452:Receptors, IgG / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D019002:CD56 Antigen; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG; D007371:Interferon-gamma