title: The bone marrow microenvironment is a critical player in the NK cell response against acute myeloid leukaemia in vitro.
abstract: Immune therapy for acute myeloid leukaemia (AML) has been largely disappointing. One possible explanation might lie in the microenvironment of the bone marrow, comprising cellular (e.g. mesenchymal stromal cells, MSC) and non-cellular components (e.g. hypoxia). The purpose of this study was to investigate the effects of these components in the immune response against AML in vitro. In vitro exposure of lymphocytes to hypoxia resulted in an increased expression of CD69 as an activation marker in NK cells only, with subsequently enhanced cell lysis of K-562 cell line by NK cells but not in lysis of primary blast. However, co-culture of AML cells with MSC significantly protected leukemic blasts from NK cell mediated lysis, mainly in a specific manner requiring cell-to-cell contact with supportive MSC. These data imply a relevant but unequivocal role of hypoxia and MSC the immune response against AML blasts.
authors.affiliation: Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Vasold
authors.affiliation: Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Wagner
authors.affiliation: Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany.
authors.forename: Heidrun
authors.initials: H
authors.lastname: Drolle
authors.affiliation: Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Deniffel
authors.affiliation: Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kütt
authors.affiliation: Department of Internal Medicine III, Hospital of the Technical University of Munich, Munich, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Oostendorp
authors.affiliation: Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sironi
authors.affiliation: Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Rieger
authors.affiliation: Department of Internal Medicine III, Hospital of the University of Munich, Munich, Germany. Electronic address: michael.fiegl@med.uni-muenchen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Fiegl
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology; D002450:Cell Communication / Q000276:immunology*; D015687:Cell Hypoxia / Q000276:immunology; D018922:HL-60 Cells; D006801:Humans; D007111:Immunity, Cellular; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000473:pathology; D051379:Mice; D059016:Tumor Microenvironment / Q000276:immunology*
keywords: Acute myeloid leukaemia; Hypoxia; Immune response; Mesenchymal stromal cells; NK cells