title: Dendritic cell-mediated survival signals in Eμ-Myc B-cell lymphoma depend on the transcription factor C/EBPβ.
abstract: The capacity of dendritic cells (DCs) to regulate tumour-specific adaptive immune responses depends on their proper differentiation and homing status. Whereas DC-associated tumour-promoting functions are linked to T-cell tolerance and formation of an inflammatory milieu, DC-mediated direct effects on tumour growth have remained unexplored. Here we show that deletion of DCs substantially delays progression of Myc-driven lymphomas. Lymphoma-exposed DCs upregulate immunomodulatory cytokines, growth factors and the CCAAT/enhancer-binding protein β (C/EBPβ). Moreover, Eμ-Myc lymphomas induce the preferential translation of the LAP/LAP* isoforms of C/EBPβ. C/EBPβ(-/-) DCs are unresponsive to lymphoma-associated cytokine changes and in contrast to wild-type DCs, they are unable to mediate enhanced Eμ-Myc lymphoma cell survival. Antigen-specific T-cell proliferation in lymphoma-bearing mice is impaired; however, this immune suppression is reverted by the DC-restricted deletion of C/EBPβ. Thus, we show that C/EBPβ-controlled DC functions are critical steps for the creation of a lymphoma growth-promoting and -immunosuppressive niche.
authors.affiliation: 1] Department of Hematology, Oncology and Tumorimmunology, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany [2] Department of Hematology and Oncology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Rehm
authors.affiliation: Department of Hematology, Oncology and Tumorimmunology, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany.
authors.forename: Marcel
authors.initials: M
authors.lastname: Gätjen
authors.affiliation: Department of Hematology, Oncology and Tumorimmunology, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Gerlach
authors.affiliation: Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Scholz
authors.affiliation: 1] Department of Hematology, Oncology and Tumorimmunology, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany [2].
authors.forename: Angela
authors.initials: A
authors.lastname: Mensen
authors.affiliation: Department of Hematology, Oncology and Tumorimmunology, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany.
authors.forename: Marleen
authors.initials: M
authors.lastname: Gloger
authors.affiliation: Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Heinig
authors.affiliation: Department of Hematology, Oncology and Tumorimmunology, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany.
authors.forename: Björn
authors.initials: B
authors.lastname: Lamprecht
authors.affiliation: 1] Department of Hematology, Oncology and Tumorimmunology, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany [2] Department of Hematology and Oncology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Mathas
authors.affiliation: Department of Cell Differentiation and Tumorigenesis, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bégay
authors.affiliation: Department of Cell Differentiation and Tumorigenesis, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany.
authors.forename: Achim
authors.initials: A
authors.lastname: Leutz
authors.affiliation: Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Lipp
authors.affiliation: 1] Department of Hematology, Oncology and Tumorimmunology, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany [2] Department of Hematology and Oncology, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, 13353 Berlin, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.affiliation: Department of Tumor Genetics and Immunogenetics, Max-Delbrück-Center for Molecular Medicine, MDC, 13125 Berlin, Germany.
authors.forename: Uta E
authors.initials: UE
authors.lastname: Höpken
mesh_terms: D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000276:immunology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002470:Cell Survival; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016274:Oncogene Protein p55(v-myc) / Q000235:genetics / Q000276:immunology*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D016274:Oncogene Protein p55(v-myc)