Dendritic cell-mediated survival signals in Eμ-Myc B-cell lymphoma depend on the transcription factor C/EBPβ
Authors
- A. Rehm
- M. Gätjen
- K. Gerlach
- F. Scholz
- A. Mensen
- M. Gloger
- K. Heinig
- B. Lamprecht
- S. Mathas
- V. Bégay
- A. Leutz
- M. Lipp
- B. Dörken
- U.E. Höpken
Journal
- Nature Communications
Citation
- Nat Commun 5: 5057
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.