Tumors suppress in situ proliferation of cytotoxic T cells by promoting differentiation of Gr-1(+) conventional dendritic cells through IL-6.
J Immunol
; 186(9): 5058-67, 2011 May 01.
Article
en En
| MEDLINE
| ID: mdl-21430223
ABSTRACT
Cancers are often accompanied by inflammation, which can promote tumor growth, invasion, and metastases. We show that the tumor microenvironment induces the development of a Gr-1(+) conventional dendritic cell (cDC) subpopulation that is functionally defective. Gr-1(+)cDCs differentiated from recruited immediate precursors of cDCs, a process supported by the inflammatory cytokine milieu in tumors. Inhibition of Gr-1(+)cDC differentiation enhanced intratumor expansion of cytotoxic CD8(+) T cells (CTLs), resulting in suppression of tumor growth. Diphtheria toxin treatment of CD11c-diphtheria toxin receptor chimeras revealed the importance of intratumor cDCs in stimulating CTL proliferation in situ. Our study demonstrates a key role of intratumor cDCs in determining antitumor CTL responses and suggests that they may be an appropriate target for tumor immunotherapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Linfocitos T Citotóxicos
/
Diferenciación Celular
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Interleucina-6
/
Proliferación Celular
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Microambiente Tumoral
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Neoplasias Experimentales
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2011
Tipo del documento:
Article
País de afiliación:
Canadá