Killer Ig-like receptors (KIRs): Their role in NK cell modulation and developments leading to their clinical exploitation

Daniela Pende, Michela Falco, Massimo Vitale, Claudia Cantoni, Chiara Vitale, Enrico Munari, Alice Bertaina, Francesca Moretta, Genny Del Zotto, Gabriella Pietra, Maria Cristina Mingari, Franco Locatelli, Lorenzo Moretta

Risultato della ricerca: Contributo in rivistaArticolo in rivista


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.
Lingua originaleEnglish
pagine (da-a)1-18
Numero di pagine18
RivistaFrontiers in Immunology
Stato di pubblicazionePubblicato - 2019


  • HLA class I
  • Inhibitory checkpoints
  • Killer immunoglobulin-like receptors
  • Polymorphism
  • NK alloreactivity
  • NK cell education
  • KIR ligands


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