Cytotoxicity of Human Hepatic Intrasinusoidal CD56bright Natural Killer Cells against Hepatocellular Carcinoma Cells

Int J Mol Sci. 2019 Mar 28;20(7):1564. doi: 10.3390/ijms20071564.

Abstract

Hepatic intrasinusoidal (HI) natural killer (NK) cells from liver perfusate have unique features that are similar to those of liver-resident NK cells. Previously, we have reported that HI CD56bright NK cells effectively degranulate against SNU398 hepatocellular carcinoma (HCC) cells. Thus, the aim of this study was to further investigate the phenotype and function of HI NK cells. We found that HI CD56bright NK cells degranulated much less to Huh7 cells. HI CD56bright NK cells expressed NKG2D, NKp46, TNF-related apoptosis-inducing ligand (TRAIL), and FAS ligand (FASL) at higher levels than CD56dim cells. SNU398 cells expressed more NKG2D ligands and FAS and less PD-L1 than Huh7 cells. Blockade of NKG2D, TRAIL, and FASL significantly reduced the cytotoxicity of HI NK cells against SNU398 cells, but blockade of PD-L1 did not lead to any significant change. However, HI NK cells produced IFN-γ well in response to Huh7 cells. In conclusion, the cytotoxicity of HI CD56bright NK cells was attributed to the expression of NKG2D, TRAIL, and FASL. The results suggest the possible use of HI NK cells for cancer immunotherapy and prescreening of HCC cells to help identify the most effective NK cell therapy recipients.

Keywords: CD56bright NK cells; FASL; NKG2D; TRAIL; cancer immunotherapy; cytotoxicity; hepatic intrasinusoidal NK cells; hepatocellular carcinoma; liver-associated NK cells.

MeSH terms

  • Adult
  • CD56 Antigen / analysis
  • CD56 Antigen / immunology*
  • Carcinoma, Hepatocellular / immunology*
  • Cell Line, Tumor
  • Fas Ligand Protein / analysis
  • Fas Ligand Protein / immunology
  • Female
  • GPI-Linked Proteins / analysis
  • GPI-Linked Proteins / immunology
  • Humans
  • Intercellular Signaling Peptides and Proteins / analysis
  • Intercellular Signaling Peptides and Proteins / immunology
  • Interferon-gamma / analysis
  • Interferon-gamma / immunology
  • Killer Cells, Natural / immunology*
  • Liver Neoplasms / immunology*
  • Male
  • TNF-Related Apoptosis-Inducing Ligand / analysis
  • TNF-Related Apoptosis-Inducing Ligand / immunology

Substances

  • CD56 Antigen
  • FASLG protein, human
  • Fas Ligand Protein
  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • NCAM1 protein, human
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • ULBP2 protein, human
  • Interferon-gamma