TY - JOUR
T1 - Killer Ig-like receptors (KIRs): 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
PY - 2019
Y1 - 2019
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.
KW - HLA class I
KW - Inhibitory checkpoints
KW - Killer immunoglobulin-like receptors
KW - Polymorphism
KW - NK alloreactivity
KW - NK cell education
KW - KIR ligands
KW - HLA class I
KW - Inhibitory checkpoints
KW - Killer immunoglobulin-like receptors
KW - Polymorphism
KW - NK alloreactivity
KW - NK cell education
KW - KIR ligands
UR - http://hdl.handle.net/10807/229990
U2 - 10.3389/fimmu.2019.01179
DO - 10.3389/fimmu.2019.01179
M3 - Article
SN - 1664-3224
VL - 10
SP - 1
EP - 18
JO - Frontiers in Immunology
JF - Frontiers in Immunology
ER -