Decreased expression of DNAM‐1 on NK cells from acute myeloid leukemia patients
- 8 March 2011
- journal article
- research article
- Published by Wiley in Immunology & Cell Biology
- Vol. 90 (1), 109-115
- https://doi.org/10.1038/icb.2011.15
Abstract
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. Immunology and Cell Biology (2012) 90, 109-115; doi: 10.1038/icb.2011.15; published online 8 March 2011Keywords
Funding Information
- Ministry of Education and Science of Spain (SAF2006-03687, SAF2009-09711)
This publication has 34 references indexed in Scilit:
- Natural Killer Cells in Innate Immunity and CancerJournal of Immunotherapy, 2008
- Human natural killer cellsBlood, 2008
- NK cell receptors and their ligands in leukemiaLeukemia, 2007
- The NKG2D receptor: immunobiology and clinical implicationsImmunologic Research, 2007
- Activation, coactivation, and costimulation of resting human natural killer cellsImmunological Reviews, 2006
- Lymphocyte activation in response to melanoma: interaction of NK-associated receptors and their ligandsCancer Immunology, Immunotherapy, 2006
- Natural Killer Cell-Mediated Killing of Freshly Isolated Neuroblastoma CellsCancer Research, 2004
- CD226 Mediates Platelet and Megakaryocytic Cell Adhesion to Vascular Endothelial CellsJournal of Biological Chemistry, 2003
- Identification of PVR (CD155) and Nectin-2 (CD112) as Cell Surface Ligands for the Human DNAM-1 (CD226) Activating MoleculeThe Journal of Experimental Medicine, 2003
- DNAM-1, A Novel Adhesion Molecule Involved in the Cytolytic Function of T LymphocytesImmunity, 1996