Dendritic cell-mediated survival signals in Eµ-Myc B-cell lymphoma depend on the transcription factor C/EBPß.
Nat Commun
; 5: 5057, 2014 Sep 30.
Article
en En
| MEDLINE
| ID: mdl-25266931
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 ß (C/EBPß). Moreover, Eµ-Myc lymphomas induce the preferential translation of the LAP/LAP* isoforms of C/EBPß. C/EBPß(-/-) 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/EBPß. Thus, we show that C/EBPß-controlled DC functions are critical steps for the creation of a lymphoma growth-promoting and -immunosuppressive niche.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Linfoma de Células B
/
Proteína Oncogénica p55(v-myc)
/
Proteína beta Potenciadora de Unión a CCAAT
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Alemania