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Dendritic cell-mediated survival signals in Eμ-Myc B-cell lymphoma depend on the transcription factor C/EBPβ

Item Type:Article
Title:Dendritic cell-mediated survival signals in Eμ-Myc B-cell lymphoma depend on the transcription factor C/EBPβ
Creators Name:Rehm, A., Gätjen, M., Gerlach, K., Scholz, F., Mensen, A., Gloger, M., Heinig, K., Lamprecht, B., Mathas, S., Bégay, V., Leutz, A., Lipp, M., Dörken, B. and Höpken, U.E.
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.
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
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:5057
Date:30 September 2014
Official Publication:https://doi.org/10.1038/ncomms6057
PubMed:View item in PubMed

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