Functional impairment in circulating and intrahepatic NK cells and relative mechanism in hepatocellular carcinoma patients

Clin Immunol. 2008 Dec;129(3):428-37. doi: 10.1016/j.clim.2008.08.012. Epub 2008 Sep 27.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD56 Antigen / immunology
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / immunology*
  • Case-Control Studies
  • Cytotoxicity Tests, Immunologic
  • Female
  • GPI-Linked Proteins
  • Humans
  • Interferon-gamma / biosynthesis
  • K562 Cells
  • Killer Cells, Natural / immunology*
  • Liver / immunology
  • Liver Neoplasms / blood
  • Liver Neoplasms / immunology*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Male
  • Middle Aged
  • Receptors, IgG / immunology
  • T-Lymphocytes, Regulatory / immunology


  • CD56 Antigen
  • FCGR3B protein, human
  • GPI-Linked Proteins
  • Receptors, IgG
  • Interferon-gamma