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

Nat Commun. 2014 Sep 30:5:5057. doi: 10.1038/ncomms6057.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CCAAT-Enhancer-Binding Protein-beta / genetics
  • CCAAT-Enhancer-Binding Protein-beta / immunology*
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Survival
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Humans
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / physiopathology
  • Mice
  • Mice, Inbred C57BL
  • Oncogene Protein p55(v-myc) / genetics
  • Oncogene Protein p55(v-myc) / immunology*

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • Oncogene Protein p55(v-myc)