This article is part of the Research Topic Proceedings of ICI Milan 2013

Mini Review ARTICLE

Front. Immunol., 07 March 2014 | http://dx.doi.org/10.3389/fimmu.2014.00087

Human NK cells: from surface receptors to the therapy of leukemias and solid tumors

  • 1Istituto Giannina Gaslini, Genova, Italy
  • 2Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genova, Genova, Italy
  • 3IRCCS AOU San Martino-IST, Genova, Italy
  • 4Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy
  • 5Università di Pavia, Pavia, Italy

Natural Killer (NK) cells are major effector cells of the innate immunity. The discovery, over two decades ago, of major histocompatibility complex-class I-specific inhibitory NK receptors and subsequently of activating receptors, recognizing ligands expressed by tumor or virus-infected cells, paved the way to our understanding of the mechanisms of selective recognition and killing of tumor cells. Although NK cells can efficiently kill tumor cells of different histotypes in vitro, their activity may be limited in vivo by their inefficient trafficking to tumor lesions and by the inhibition of their function induced by tumor cells themselves and by the tumor microenvironment. On the other hand, the important role of NK cells has been clearly demonstrated in the therapy of high risk leukemias in the haploidentical hematopoietic stem cell (HSC) transplantation setting. NK cells derived from donor HSC kill leukemic cells residual after the conditioning regimen, thus preventing leukemia relapses. In addition, they also kill residual dendritic cells and T lymphocytes, thus preventing both GvH disease and graft rejection.

Keywords: NK cells, killer Ig-like receptors, alloreactive NK cells, activating NK receptors, hematopoietic stem cell transplantation, acute leukemias, tumor microenvironment

Citation: Moretta L, Pietra G, Montaldo E, Vacca P, Pende D, Falco M, Del Zotto G, Locatelli F, Moretta A and Mingari MC (2014) Human NK cells: from surface receptors to the therapy of leukemias and solid tumors. Front. Immunol. 5:87. doi: 10.3389/fimmu.2014.00087

Received: 09 January 2014; Paper pending published: 15 January 2014;
Accepted: 19 February 2014; Published online: 07 March 2014.

Edited by:

Kendall A. Smith, Weill Medical College of Cornell University, USA

Reviewed by:

Roland Jacobs, Hannover Medical University, Germany
Bent Rolstad, University of Oslo, Norway
Vincent Vieillard, Institut National de la Santé et de la Recherche Scientifique, France

Copyright: © 2014 Moretta, Pietra, Montaldo, Vacca, Pende, Falco, Del Zotto, Locatelli, Moretta and Mingari. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Lorenzo Moretta, Istituto Giannina Gaslini, Via G. Gaslini n.5, Genova 16147, Italy e-mail: lorenzomoretta@ospedale-gaslini.ge.it