title: Human NK cells: from surface receptors to the therapy of leukemias and solid tumors.
abstract: Natural Killer (NK) cells are major effector cells of the innate immunity. The discovery, over two decades ago, of major histocompatibility complex-class I-specific inhibitory NK receptors and subsequently of activating receptors, recognizing ligands expressed by tumor or virus-infected cells, paved the way to our understanding of the mechanisms of selective recognition and killing of tumor cells. Although NK cells can efficiently kill tumor cells of different histotypes in vitro, their activity may be limited in vivo by their inefficient trafficking to tumor lesions and by the inhibition of their function induced by tumor cells themselves and by the tumor microenvironment. On the other hand, the important role of NK cells has been clearly demonstrated in the therapy of high risk leukemias in the haploidentical hematopoietic stem cell (HSC) transplantation setting. NK cells derived from donor HSC kill leukemic cells residual after the conditioning regimen, thus preventing leukemia relapses. In addition, they also kill residual dendritic cells and T lymphocytes, thus preventing both GvH disease and graft rejection.
authors.affiliation: Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genova , Genova , Italy ; IRCCS AOU San Martino-IST , Genova , Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pietra
authors.affiliation: Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genova , Genova , Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Montaldo
authors.affiliation: Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genova , Genova , Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Vacca
authors.affiliation: IRCCS AOU San Martino-IST , Genova , Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pende
authors.affiliation: Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Falco
authors.affiliation: Istituto Giannina Gaslini , Genova , Italy.
authors.forename: Genny
authors.initials: G
authors.lastname: Del Zotto
authors.affiliation: Department of Pediatric Hematology and Oncology, IRCCS Ospedale Pediatrico Bambino Gesù , Rome , Italy ; Università di Pavia , Pavia , Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genova , Genova , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.affiliation: Department of Experimental Medicine and Center of Excellence for Biomedical Research, University of Genova , Genova , Italy ; IRCCS AOU San Martino-IST , Genova , Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Mingari
keywords: NK cells; activating NK receptors; acute leukemias; alloreactive NK cells; hematopoietic stem cell transplantation; killer Ig-like receptors; tumor microenvironment