title: Kinetics of Cytotoxic Lymphocytes Reconstitution after Induction Chemotherapy in Elderly AML Patients Reveals Progressive Recovery of Normal Phenotypic and Functional Features in NK Cells.
abstract: NK cells are defective in acute myeloid leukemia (AML) at diagnosis. Here, we studied the kinetic of expression of the major activating and inhibitory receptors of NK, CD8 T, and γδ T cells in patients undergoing chemotherapy (CT) for the treatment of AML (n= 29). We showed that NK cells are the main affected population at diagnosis and that expression of activating receptors is partially restored within a few weeks after CT. CD8 T cells and γδ T cells are only weakly affected at diagnosis. Killer cell immunoglobulin-like receptor expression by NK cells, but not NKG2A and CD85j, was downregulated. Interestingly, the development of NK cells appeared altered as the most immature CD56brightNK cells were seriously underrepresented. Finally, we showed that NK cell functions were only partially restored 6 weeks after CT as degranulation capabilities of NK cells recovered, whereas cytokine production remained low. Our data point out NK cells as antitumor effectors peculiarly hampered by leukemic cells. This study may indicate a timeline when NK-mediated therapies or other immunotherapies could be performed, particularly for patients excluded of hematopoietic stem cell transplantation.
authors.affiliation: Département d'Hématologie, Institut Paoli-Calmettes, Marseille, France; Plateforme d'Immunomonitoring en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Rey
authors.affiliation: Plateforme d'Immunomonitoring en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, INSERM U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM105, CNRS, UMR7258, Marseille, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Fauriat
authors.affiliation: Plateforme d'Immunomonitoring en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, INSERM U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM105, CNRS, UMR7258, Marseille, France.
authors.forename: Eloïse
authors.initials: E
authors.lastname: Kochbati
authors.affiliation: Plateforme d'Immunomonitoring en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, INSERM U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM105, CNRS, UMR7258, Marseille, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Orlanducci
authors.affiliation: Département d'Hématologie, Institut Paoli-Calmettes , Marseille , France.
authors.forename: Aude
authors.initials: A
authors.lastname: Charbonnier
authors.affiliation: Département d'Hématologie, Institut Paoli-Calmettes , Marseille , France.
authors.forename: Evelyne
authors.initials: E
authors.lastname: D'Incan
authors.affiliation: Innate-Pharma , Marseille , France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Andre
authors.affiliation: Innate-Pharma, Marseille, France; Mi-mAbs, Aix-Marseille Université, Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Romagne
authors.affiliation: Plateforme d'Immunomonitoring en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, INSERM U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM105, CNRS, UMR7258, Marseille, France.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Barbarat
authors.affiliation: Département d'Hématologie, Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, INSERM U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM105, CNRS, UMR7258, Marseille, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Vey
authors.affiliation: Plateforme d'Immunomonitoring en Cancérologie de Marseille, Institut Paoli-Calmettes, Marseille, France; Centre de Recherche en Cancérologie de Marseille, INSERM U1068, Institut Paoli-Calmettes, Aix-Marseille Université, UM105, CNRS, UMR7258, Marseille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
keywords: NK cells; NK functions; activating receptors; acute myeloid leukemia; chemotherapy