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


  • 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


  • Nature Communications


  • Nat Commun 5: 5057


  • 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.