Immunoproteasome down-modulation enhances the ability of dendritic cells to stimulate antitumor immunity.
Blood
; 110(13): 4341-50, 2007 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-17855630
ABSTRACT
The process of dendritic cell (DC) maturation, critical for effective DC-based immunotherapy, also alters the proteasome such that peptides presented in the context of HLA class I are generated not by the constitutive proteasome, but by the immunoproteasome. Cytotoxic T lymphocytes (CTLs) induced by such DCs might not optimally recognize tumor cells normally expressing the constitutive proteasome. Using small interfering RNA (siRNA) transfection of DCs to inhibit expression of the 3 inducible immunoproteasome subunits in mature DCs, we found that such DCs expressed increased intracellular levels of constitutive proteasomes and presented an altered repertoire of tumor-antigenic peptides. When DCs generated from the monocytes of 3 patients with melanoma were transfected with immunoproteasome siRNA, induced to mature, and then trans-fected with RNA encoding defined melanoma antigens, these DCs were superior inducers of antigen-specific CTLs against autologous melanoma cells. This alteration of DC proteasome composition, which enhances the ability of mature antigen-loaded DCs to stimulate anti-tumor immune responses, may lead to more effective DC-based tumor immunotherapy.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Linfocitos T Citotóxicos
/
Complejo de la Endopetidasa Proteasomal
/
Melanoma
/
Antígenos de Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Blood
Año:
2007
Tipo del documento:
Article
País de afiliación:
Estados Unidos