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Dendritic cell-mediated survival signals in E{my}-Myc B-cell lymphoma depend on the transcription factor C/EBP{beta}

Official URL:https://doi.org/10.1038/ncomms6057
PubMed:View item in PubMed
Creators Name:Rehm, A. and Gaetjen, M. and Gerlach, K. and Scholz, F. and Mensen, A. and Gloger, M. and Heinig, K. and Lamprecht, B. and Mathas, S. and Begay, V. and Leutz, A. and Lipp, M. and Doerken, B. and Hoepken, U.E.
Journal Title:Nature Communications
Journal Abbreviation:Nat Commun
Volume:5
Page Range:5057
Date:30 September 2014
Keywords:B-Cell Lymphoma, CCAAT-Enhancer-Binding Protein-beta, Cell Differentiation, Cell Survival, Dendritic Cells, Oncogene Protein p55(v-myc), Tumor Cell Line, Animals, Mice
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 {beta} (C/EBP{beta}). Moreover, Eμ-Myc lymphomas induce the preferential translation of the LAP/LAP* isoforms of C/EBP{beta}. C/EBP{beta}(-/-) DCs are unresponsive to lymphoma-associated cytokine changes and in contrast to wild-type DCs, they are unable to mediate enhanced E{my}-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/EBP{beta}. Thus, we show that C/EBP{beta}-controlled DC functions are critical steps for the creation of a lymphoma growth-promoting and -immunosuppressive niche.
ISSN:2041-1723
Publisher:Nature Publishing Group (U.K.)
Item Type:Article

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