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

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, E μ -Myc lymphomas induce the preferential translation of the LAP/LAP* isoforms of C/EBPβ. C/EBP β −/− DCs are unresponsive to lymphoma-associated cytokine changes and in contrast to wild-type DCs, they are unable to mediate enhanced E μ -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 β. Thus, we show that C/EBPβ-controlled DC functions are critical steps for the creation of a lymphoma growth-promoting and -immunosuppressive niche.