title: Critical role of the NKG2D receptor for NK cell-mediated control and immune escape of B-cell lymphoma.
abstract: Little is known on the control of lymphomas by NK cells. Here, we study the role of the NK group 2D (NKG2D) receptor for the immunosurveillance of lymphoma. By using transplantable tumors as well as a λ-myc-transgenic model of endogenously arising lymphoma and NKG2D-deficient mice, we show that NK cells eliminate tumor cells in vivo after receiving two signals. One step involved the activation of NK cells giving rise to IFN-γ expression, which was effected by MHCI(low) tumor cells or DCs. However, this was necessary but not sufficient to mediate cytotoxicity. Triggering cytotoxicity additionally required a second step, which could be mediated by engagement of the NKG2D receptor. Thus, NKG2D-deficient NK cells could become activated in vivo, but they were not able to reject transplanted lymphomas or to degranulate in animals bearing autochthonous lymphomas. Tumor growth in NKG2D-deficient λ-myc-transgenic mice was significantly accelerated compared to NKG2D-competent animals. Whereas the latter developed tumors that lost expression of NKG2D ligands (NKG2D-L) in late disease stages, this did not occur in NKG2D-deficient mice. This indicates that NK cells and the NKG2D receptor play a role for control of lymphomas and that selection for NKG2D-L loss mutants provides a mechanism of tumor escape.
authors.affiliation: Institut für Molekulare Immunologie, Helmholtz-Zentrum München, München, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Belting
authors.affiliation: Institut für Molekulare Immunologie, Helmholtz-Zentrum München, München, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Hömberg
authors.affiliation: Institut für Molekulare Immunologie, Helmholtz-Zentrum München, München, Germany.
authors.forename: Margarethe
authors.initials: M
authors.lastname: Przewoznik
authors.affiliation: Institut für Molekulare Immunologie, Helmholtz-Zentrum München, München, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Brenner
authors.affiliation: Institut für Molekulare Immunologie, Helmholtz-Zentrum München, München, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Riedel
authors.affiliation: Institut für Molekulare Immunologie, Helmholtz-Zentrum München, München, Germany.
authors.forename: Andrew
authors.initials: A
authors.lastname: Flatley
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia.
authors.forename: Bojan
authors.initials: B
authors.lastname: Polić
authors.affiliation: Institut für Medizinische Mikrobiologie, Immunologie und Hygiene, Technische Universität München, München, Germany.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: Universitäts-Hautklinik, Eberhard-Karls-Universität, Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Röcken
authors.affiliation: Institut für Molekulare Immunologie, Helmholtz-Zentrum München, München, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Mocikat
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D015972:Gene Expression Regulation, Neoplastic; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008565:Membrane Proteins; D051379:Mice; D008822:Mice, Transgenic; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000276:immunology*; D009368:Neoplasm Transplantation; D015398:Signal Transduction; D019139:Tumor Escape / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; C468260:UL16 binding protein 1, mouse; D007371:Interferon-gamma
keywords: Endogenous B-cell lymphoma; NK-cell activation; NKG2D ligands; Tumor escape; λ-myc mouse