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Human NK cells in acute myeloid leukaemia patients: analysis of NK cell-activating receptors and their ligands

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Abstract

Natural killer (NK) cell activation is strictly regulated to ensure that healthy cells are preserved, but tumour-transformed or virus-infected cells are recognized and eliminated. To carry out this selective killing, NK cells have an ample repertoire of receptors on their surface. Signalling by inhibitory and activating receptors by interaction with their ligands will determine whether the NK cell becomes activated and kills the target cell. Here, we show reduced expression of NKp46, NKp30, DNAM-1, CD244 and CD94/NKG2C activating receptors on NK cells from acute myeloid leukaemia patients. This reduction may be induced by chronic exposure to their ligands on leukaemic blasts. The analysis of ligands for NK cell-activating receptors showed that leukaemic blasts from the majority of patients express ligands for NK cell-activating receptors. DNAM-1 ligands are frequently expressed on blasts, whereas the expression of the NKG2D ligand MICA/B is found in half of the patients and CD48, a ligand for CD244, in only one-fourth of the patients. The decreased expression of NK cell-activating receptors and/or the heterogeneous expression of ligands for major receptors on leukaemic blasts can lead to an inadequate tumour immunosurveillance by NK cells. A better knowledge of the activating receptor repertoire on NK cells and their putative ligands on blasts together with the possibility to modulate their expression will open new possibilities for the use of NK cells in immunotherapy against leukaemia.

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Acknowledgments

We apologize to our colleagues whose work was not cited due to space limitations. This work was supported by grants SAF2006-03687 and SAF2009-09711 (to RT) from the Ministry of Science and Innovation of Spain, FIS PI061320 and PS09/00723 (to R.S.) from Spanish Ministry of Health, PRI09A029 and grants to INPATT research group from Junta de Extremadura (GRU08077, GRU09156 and GRU10104) and from University of Extremadura, cofinanced by European Regional Development Fund (FEDER). BSC is a postdoctoral fellow supported by grant ACCIII/22 from University of Extremadura Spain, and SM is a predoctoral fellow supported by grant PRE07047 from Junta de Extremadura. We thank J.J. Gordillo and M.R. Gonzalez and for their technical assistance in cell culture and flow cytometry.

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Correspondence to Raquel Tarazona.

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Beatriz Sanchez-Correa and Sara Morgado contributed equally to the manuscript.

This paper is a Focussed Research Review based on a presentation given at the Tenth International Conference on Progress in Vaccination against Cancer (PIVAC 10), held in St. Catharine’s College, Cambridge, UK, 27th–30th September 2010. It is part of a CII series of Focussed Research Reviews and meeting report.

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Sanchez-Correa, B., Morgado, S., Gayoso, I. et al. Human NK cells in acute myeloid leukaemia patients: analysis of NK cell-activating receptors and their ligands. Cancer Immunol Immunother 60, 1195–1205 (2011). https://doi.org/10.1007/s00262-011-1050-2

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