Tumors hamper the immunogenic competence of CD4+ T cell-directed dendritic cell vaccination.
J Immunol
; 179(5): 2899-909, 2007 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-17709504
ABSTRACT
Dendritic cells loaded with tumor-derived peptides induce protective CTL responses and are under evaluation in clinical trails. We report in this study that prophylactic administration of dendritic cells loaded with a MHC class II-restricted peptide derived from a model tumor Ag (Leishmania receptor for activated C kinase (LACK)) confers protection against LACK-expressing TS/A tumors, whereas therapeutic vaccination fails to cure tumor-bearing mice. Although CD4+ T cell-directed dendritic cell vaccination primed effector-like (CD44(high)CD62L(low), IL-2(+), IFN-gamma(+)) and central memory-like lymphocytes (CD44(high)CD62L(high), only IL-2(+)) in tumor-free mice, this was not the case in tumor-bearing animals in which both priming and persistence of CD4+ T cell memory were suppressed. Suppression was specific for the tumor-associated Ag LACK, and did not depend on CD25+ T cells. Because T cell help is needed for protective immunity, we speculate that the ability of tumors to limit vaccine-induced CD4+ T cell memory could provide a partial explanation for the limited efficacy of current strategies.
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Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
/
4_TD
Base de dados:
MEDLINE
Assunto principal:
Células Dendríticas
/
Antígenos de Histocompatibilidade Classe II
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Proteínas de Protozoários
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Vacinação
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Antígenos de Protozoários
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Neoplasias
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2007
Tipo de documento:
Article