Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Review J Innate Immun 2011;3:383–394 DOI: 10.1159/000323935 Role of Natural Killer Cells in Hematopoietic Stem Cell Transplantation: Myth or Reality? Stéphanie Nguyen   a–c Vivien Béziat   a, c Damien Roos-Weil   b Vincent Vieillard   a, c a  INSERM UMR-S 945 and b  Service d’Hématologie Clinique, Hôpital Pitié-Salpêtrière, and c  Université Pierre et Marie Curie, Paris, France lack of suitable donors constitutes one of the major limitations to successful transplantation, because ap- proximately only one third of candidates for allogeneic HSCT have human leukocyte antigen (HLA)-matched siblings. For those patients, alternative sources of stem cells for allogeneic HSCT include matched unrelated volunteers, umbilical cord blood and partially HLA mismatched or HLA haploidentical donors. Cure of ma- lignancies by HSCT relies on the ability of the immune cells in the graft to recognize and eliminate the leuke- mia cells. Donor alloreactive T cells are the main effec- tors of the graft-versus-leukemia (GvL) effect and are directed against minor or major histocompatibility molecules. Unfortunately, these molecules are not only shared by leukemic cells, but also by normal host cells, resulting in graft-versus-host disease (GvHD), a lethal complication that limits the wider application of alloge- neic HSCT. In these settings, natural killer (NK) cells may play a crucial role in achieving successful transplantation. In- deed, contrary to T cells, NK cells recover very quickly after HSCT and may mediate a strong GvL effect with- out inducing acute GvHD (aGvHD), a dissociate effect that represents the ultimate goal for HSCT. This review will focus on various aspects of donor-derived NK cells in patients with leukemia receiving haploidentical HSCT. Key Words Natural killer cells  Hematopoietic transplantation  Graft-versus-leukemia effect  Clinical outcome Abstract Natural killer (NK) cells play a crucial role in the innate im- mune system and are responsible for the initial responses in the surveillance against malignant cells and virally infected cells. NK cells express their own repertoire of receptors, in- cluding activating and inhibitory receptors, which bind to major histocompatibility complex class I or class-I-related molecules. Binding of NK cell inhibitory receptors to their major histocompatibility complex class I ligands protects the target cells from NK cell-mediated cytotoxicity. NK cell allo- reactivity has been put to use in allogeneic hematopoietic stem cell transplantation to reduce the rate of relapse and of graft-versus-host disease. A variety of findings have been observed in clinical studies, showing either beneficial or del- eterious effects on clinical outcome. This article reviews the results of major clinical trials in relation to the model used to define NK cell alloreactivity. Copyright © 2011 S. Karger AG, Basel Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for a variety of high-risk hematologic malignancies. Unfortunately, the Received: November 6, 2010 Accepted after revision: December 24, 2010 Published online: March 12, 2011 Journal of Innate Immunity Dr. Vincent Vieillard INSERM UMR-S 945, Hôpital Pitié-Salpêtrière 83 Boulevard de l’Hôpital FR–75013 Paris (France) Tel. +33 14 217 7524, E-Mail vincent.vieillard  @  upmc.fr © 2011 S. Karger AG, Basel 1662–811X/11/0034–0383$38.00/0 Accessible online at: www.karger.com/jin Downloaded by: INSERM DISC IST 193.54.110.33 - 10/29/2014 9:38:50 AM