title: Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia.
abstract: The cytolytic function of natural killer (NK) cells is induced by the engagement of a series of activating receptors and coreceptors some of which have recently been identified and collectively termed natural cytotoxicity receptors (NCRs). Here, we analyzed the cytolytic function of NK cells obtained from patients with acute myeloid leukemia (AML). In sharp contrast with healthy donors, in most (16 of 18) patients with AML the majority of NK cells displayed low NCR surface density (NCR(dull)). This phenotype correlated with a weak cytolytic activity against autologous leukemic cells that could not be reversed by the monoclonal antibody-mediated disruption of HLA class I/killer immunoglobulinlike receptor interaction. The remaining 2 patients were characterized by NK cells having an NCR(bright) phenotype. Surprisingly, although displaying NCR-mediated cytolytic activity, these NCR(bright) NK cells were unable to kill autologous leukemic blasts. Importantly, the leukemic blasts from these 2 patients were also resistant to lysis mediated by normal NCR(bright) allogeneic NK cells. Our study suggests that in most instances the inability of NK cells to kill autologous leukemic blasts is consequent to low NCR surface expression. In few cases, however, this failure appears to involve a mechanism of tumor escape based on down-regulation of ligands relevant for NCR-mediated target cell recognition.
authors: Unité d'Immunologie des Tumeurs Département d'Hématologie, Institut Paoli-Calmettes, Université de la Méditerranée, Marseille, France. regis.costello@free.fr
authors: Régis T
authors: RT
authors: Costello
authors: Simona
authors: S
authors: Sivori
authors: Emanuela
authors: E
authors: Marcenaro
authors: Marina
authors: M
authors: Lafage-Pochitaloff
authors: Marie-Joelle
authors: MJ
authors: Mozziconacci
authors: Denis
authors: D
authors: Reviron
authors: Jean-Albert
authors: JA
authors: Gastaut
authors: Daniela
authors: D
authors: Pende
authors: Daniel
authors: D
authors: Olive
authors: Alessandro
authors: A
authors: Moretta
mesh_terms: D000208:Acute Disease; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000145:classification / Q000276:immunology*; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000276:immunology*; D051379:Mice; D011971:Receptors, Immunologic / Q000378:metabolism* / Q000502:physiology*; D014407:Tumor Cells, Cultured; D019139:Tumor Escape
chemical_list: D011971:Receptors, Immunologic