title: Human natural killer cells: origin, receptors, function, and clinical applications.
abstract: Natural killer (NK) cells are important effectors playing a relevant role in innate immunity, primarily in tumor surveillance and in defenses against viruses. Human NK cells recognize HLA class I molecules through surface receptors (KIR and NKG2A) that inhibit NK cell function and kill target cells that have lost (or underexpress) HLA class I molecules as it occurs in tumors or virus-infected cells. NK cell activation is mediated by an array of activating receptors and co-receptors that recognize ligands expressed primarily on tumors or virus-infected cells. In vivo anti-tumor NK cell activity may be suppressed by tumor or tumor-associated cells. Alloreactive NK cells (i.e. those that are not inhibited by the HLA class I alleles of the patient) derived from HSC of haploidentical donors play a major role in the cure of high-risk leukemia, by killing leukemia blasts and patient's DC, thus preventing tumor relapses and graft-versus-host disease. The expression of the HLA-C2-specific activating KIR2DS1 may also contribute to NK alloreactivity in patients expressing C2 alleles. A clear correlation has been proven between the size of the alloreactive NK cell population and the clinical outcome. Recently, haplo-HSCT has been further improved with the direct infusion, together with HSC, of donor-derived, mature alloreactive NK cells and TCRγδ(+) T cells - both contributing to a prompt anti-leukemia effect together with an efficient defense against pathogens during the 6- to 8-week interval required for the generation of alloreactive NK cells from HSC.
authors.affiliation: Istituto Giannina Gaslini, Università di Genova, Genoa, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Elisa
authors.initials: E
authors.lastname: Montaldo
authors.forename: Paola
authors.initials: P
authors.lastname: Vacca
authors.forename: Genny
authors.initials: G
authors.lastname: Del Zotto
authors.forename: Francesca
authors.initials: F
authors.lastname: Moretta
authors.forename: Pietro
authors.initials: P
authors.lastname: Merli
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
mesh_terms: D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology*; D007938:Leukemia / Q000276:immunology; D009369:Neoplasms / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology
chemical_list: D006680:HLA Antigens