In vivo blockade of CTLA-4 enhances the priming of responsive T cells but fails to prevent the induction of tumor antigen-specific tolerance.
Proc Natl Acad Sci U S A
; 96(20): 11476-81, 1999 Sep 28.
Article
em En
| MEDLINE
| ID: mdl-10500201
ABSTRACT
The efficacy of therapeutic vaccination for the treatment of cancer is limited by peripheral tolerance to tumor antigens. In vivo blockade of CTLA-4, a negative regulator of T cell function, can induce the regression of established tumors and can augment the tumor rejection achieved through therapeutic vaccination. These outcomes may reflect enhanced tumor-specific T cell priming and/or interference with the development of tolerance to tumor antigens. We examined the effect of CTLA-4 blockade on the fate and function of T cells specific for a model tumor antigen in the tumor-bearing host. We found that while CTLA-4 blockade enhanced the priming of responsive T cells, it did not prevent the induction of tolerance to tumor antigens. These results demonstrate that there is a critical window in which the combination of CTLA-4 blockade and vaccination achieves an optimal response, and they point to mechanisms other than CTLA-4 engagement in mediating peripheral T cell tolerance to tumor antigens.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Antígenos de Diferenciação
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Imunoconjugados
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Tolerância Imunológica
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Antígenos de Neoplasias
Limite:
Animals
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos