Loss of MAPK-activated protein kinase 2 enables potent dendritic cell-driven anti-tumour T cell response.
Sci Rep
; 7(1): 11746, 2017 09 18.
Article
en En
| MEDLINE
| ID: mdl-28924177
ABSTRACT
Maintaining dendritic cells (DC) in a state of dysfunction represents a key mechanism by which tumour cells evade recognition and elimination by the immune system. Limited knowledge about the intracellular mediators of DC dysfunction restricts success of therapies aimed at reactivating a DC-driven anti-tumour immune response. Using a cell type-specific murine knock-out model, we have identified MAPK-activated protein kinase 2 (MK2) as a major guardian of a suppressive DC phenotype in the melanoma tumour microenvironment. MK2 deletion in CD11c+ cells led to an expansion of stimulatory CD103+ DCs, mounting a potent CD8+ T cell response that resulted in elimination of highly aggressive B16-F10 tumours upon toll-like receptor (TLR) activation in the presence of tumour antigen. Moreover, tumour infiltration by suppressive myeloid cells was strongly diminished. These insights into the regulation of DC functionality reveal MK2 as a targetable pathway for DC-centred immunomodulatory cancer therapies.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Melanoma Experimental
/
Proteínas Serina-Treonina Quinasas
/
Linfocitos T CD8-positivos
/
Péptidos y Proteínas de Señalización Intracelular
/
Microambiente Tumoral
/
Inmunidad Celular
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2017
Tipo del documento:
Article
País de afiliación:
Austria