Killer Ig-like receptors (KIRs): their role in NK cell modulation and developments leading to their clinical exploitation
- 1Bambino Gesù Children Hospital (IRCCS), Italy
- 2IRCCS Ospedale Policlinico San Martino, Italy
- 3IRCCS Istituto G. Gaslini, Italy
- 4Università di Genova, Italy
- 5IRCCS Sacro Cuore Don Calabria Hospital, Italy
- 6Department of Pediatrics Stanford School of Medicine, United States
- 7IRCCS Ospedale Pediatrico Bambino Gesù, Italy
Natural killer (NK) cells contribute to the first line of defense against viruses and to the control of tumor growth and metastasis spread. The discovery of HLA class I specific inhibitory receptors, primarily of killer Ig-like receptors (KIRs), and of activating receptors has been fundamental to unravel NK cell function and the molecular mechanisms of tumor cell killing. Stemmed from the seminal discoveries in early ‘90s, in which Alessandro Moretta was the major actor, an extraordinary amount of research on KIR specificity, genetics, polymorphism and repertoire has followed.
These basic notions on NK cells and their receptors have been successfully translated to clinical applications, primarily to the haploidentical haematopoietic stem cell transplantation to cure otherwise fatal leukemia in patients with no HLA compatible donors. The finding that NK cells may express the PD-1 inhibitory checkpoint, particularly in cancer patients, may allow to understand how anti-PD-1 therapy could function also in case of HLA class Ineg tumors, usually susceptible to NK-mediated killing. This, together with the synergy of therapeutic anti-checkpoint monoclonal antibodies, including those directed against NKG2A or KIRs, emerging in recent or ongoing studies, opened new solid perspectives in cancer therapy.
Keywords: HLA class I, Killer immunoglobulin-like receptors, KIR ligands, Inhibitory checkpoints, NK alloreactivity, NK cell education, polymorphism
Received: 24 Mar 2019;
Accepted: 09 May 2019.
Edited by:Eric Vivier, INSERM U1104 Centre d'immunologie de Marseille-Luminy, France
Reviewed by:Salim I. Khakoo, University of Southampton, United Kingdom
Hans-Gustaf Ljunggren, Karolinska Institute (KI), Sweden
Copyright: © 2019 MORETTA, Pende, Falco, Vitale, Cantoni, Vitale, Munari, Bertaina, Moretta, Del Zotto, Pietra, Mingari and Locatelli. 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) and the copyright owner(s) 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: Prof. LORENZO MORETTA, Bambino Gesù Children Hospital (IRCCS), Rome, Italy, firstname.lastname@example.org