Killer Ig-Like Receptors (KIRs)

Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation

Research output: Contribution to journalReview article

Abstract

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 hematopoietic 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 understanding 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.

Original languageEnglish
Number of pages1
JournalFrontiers in Immunology
Volume10
DOIs
Publication statusPublished - Jan 1 2019

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Natural Killer Cells
Neoplasms
KIR Receptors
Natural Killer Cell Receptors
Hematopoietic Stem Cell Transplantation
Genetic Polymorphisms
Leukemia
Therapeutics
Monoclonal Antibodies
Tissue Donors
Neoplasm Metastasis
Viruses
Growth
Research

Keywords

  • HLA class I
  • inhibitory checkpoints
  • killer immunoglobulin-like receptors
  • KIR ligands
  • NK alloreactivity
  • NK cell education
  • polymorphism

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

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title = "Killer Ig-Like Receptors (KIRs): Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation",
abstract = "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 hematopoietic 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 understanding 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, inhibitory checkpoints, killer immunoglobulin-like receptors, KIR ligands, NK alloreactivity, NK cell education, polymorphism",
author = "Daniela Pende and Michela Falco and Massimo Vitale and Claudia Cantoni and Chiara Vitale and Enrico Munari and Alice Bertaina and Francesca Moretta and {Del Zotto}, Genny and Gabriella Pietra and Mingari, {Maria Cristina} and Franco Locatelli and Lorenzo Moretta",
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T2 - Their Role in NK Cell Modulation and Developments Leading to Their Clinical Exploitation

AU - Pende, Daniela

AU - Falco, Michela

AU - Vitale, Massimo

AU - Cantoni, Claudia

AU - Vitale, Chiara

AU - Munari, Enrico

AU - Bertaina, Alice

AU - Moretta, Francesca

AU - Del Zotto, Genny

AU - Pietra, Gabriella

AU - Mingari, Maria Cristina

AU - Locatelli, Franco

AU - Moretta, Lorenzo

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N2 - 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 hematopoietic 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 understanding 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.

AB - 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 hematopoietic 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 understanding 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.

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KW - NK alloreactivity

KW - NK cell education

KW - polymorphism

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