NKG2D Signaling Leads to NK Cell Mediated Lysis of Childhood AML

J Immunol Res. 2015:2015:473175. doi: 10.1155/2015/473175. Epub 2015 Jul 8.

Abstract

Natural killer cells have been shown to be relevant in the recognition and lysis of acute myeloid leukemia. In childhood acute lymphoblastic leukemia, it was shown that HLA I expression and KIR receptor-ligand mismatch significantly impact ALL cytolysis. We characterized 14 different primary childhood AML blasts by flow cytometry including NKG2D ligands. Further HLA I typing of blasts was performed and HLA I on the AML blasts was quantified. In two healthy volunteer NK cell donors HLA I typing and KIR genotyping were done. Blasts with high NKG2D ligand expression had significantly higher lysis by isolated NK cells. Grouping the blasts by NKG2D ligand expression led to a significant inverse correlation of HLA I expression and cytolysis in NKG2D low blasts. Furthermore, a significant positive correlation of NKG2D ligand expression and blast cytolysis was shown. No impact of KIR ligand-ligand mismatch was found but a significantly increased lysis of homozygous C2 blasts by KIR2DL1 negative NK cells (donor B) was revealed. In conclusion, NKG2D signaling leads to NK cell mediated lysis of childhood AML despite high HLA I expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Cell Line, Tumor
  • Child
  • Cytotoxicity, Immunologic*
  • Gene Expression
  • HLA-E Antigens
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Immunophenotyping
  • K562 Cells
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Leukemia, Myeloid, Acute / genetics
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / metabolism*
  • Leukemia, Myeloid, Acute / pathology
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K / genetics
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism*
  • Phenotype
  • Signal Transduction*

Substances

  • Histocompatibility Antigens Class I
  • KLRK1 protein, human
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K