Decreased expression of DNAM-1 on NK cells from acute myeloid leukemia patients

Immunol Cell Biol. 2012 Jan;90(1):109-15. doi: 10.1038/icb.2011.15. Epub 2011 Mar 8.


This study tested the hypothesis that the expression of CD112 and CD155 (DNAM-1 ligands) on leukemic blasts induces a decreased expression of the activating receptor DNAM-1 on natural killer (NK) cells from acute myeloid leukemia (AML) patients. DNAM-1 is a co-receptor involved in the activation of NK cell cytotoxicity after its interaction with its ligands CD112 and CD155 on target cells. Here we study the expression of DNAM-1 on NK cells and DNAM-1 ligands on blasts from AML patients stratified by age. The results demonstrate that NK cells from AML patients younger than 65 years have a reduced expression of DNAM-1 compared with age-matched controls. The analysis of DNAM-1 ligands showed a high expression of CD112 and CD155 on leukemic blasts. An inverse correlation between CD112 expression on leukemic blasts and DNAM-1 expression on NK cells was found. Furthermore, downregulation of DNAM-1 was induced on healthy donors' NK cells after in vitro culture with leukemic blasts expressing DNAM-1 ligands. In conclusion, these results support the hypothesis that receptor-ligand crosslinking downregulates DNAM-1 expression on NK cells from patients <65 years of age. Considering the relevance of DNAM-1 in NK recognition and killing of leukemic cells, the reduced expression of this receptor on NK cells from AML patients can represent an additional mechanism of tumor escape.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Differentiation, T-Lymphocyte / biosynthesis
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Cell Adhesion Molecules / biosynthesis
  • Cell Adhesion Molecules / immunology*
  • Cells, Cultured
  • Coculture Techniques
  • Down-Regulation / immunology
  • Female
  • Flow Cytometry
  • Humans
  • K562 Cells
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Leukemia, Myeloid / immunology*
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology
  • Ligands
  • Male
  • Middle Aged
  • Nectins
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Receptors, Virus / biosynthesis
  • Receptors, Virus / immunology*
  • Young Adult


  • Antigens, Differentiation, T-Lymphocyte
  • CD226 antigen
  • Cell Adhesion Molecules
  • Ligands
  • Nectins
  • Receptors, Virus
  • poliovirus receptor