Recruitment of latent pools of high-avidity CD8(+) T cells to the antitumor immune response.
J Exp Med
; 201(10): 1591-602, 2005 May 16.
Article
em En
| MEDLINE
| ID: mdl-15883172
ABSTRACT
A major barrier to successful antitumor vaccination is tolerance of high-avidity T cells specific to tumor antigens. In keeping with this notion, HER-2/neu (neu)-targeted vaccines, which raise strong CD8(+) T cell responses to a dominant peptide (RNEU(420-429)) in WT FVB/N mice and protect them from a neu-expressing tumor challenge, fail to do so in MMTV-neu (neu-N) transgenic mice. However, treatment of neu-N mice with vaccine and cyclophosphamide-containing chemotherapy resulted in tumor protection in a proportion of mice. This effect was specifically abrogated by the transfer of neu-N-derived CD4(+)CD25(+) T cells. RNEU(420-429)-specific CD8(+) T cells were identified only in neu-N mice given vaccine and cyclophosphamide chemotherapy which rejected tumor challenge. Tetramer-binding studies demonstrated that cyclophosphamide pretreatment allowed the activation of high-avidity RNEU(420-429)-specific CD8(+) T cells comparable to those generated from vaccinated FVB/N mice. Cyclophosphamide seemed to inhibit regulatory T (T reg) cells by selectively depleting the cycling population of CD4(+)CD25(+) T cells in neu-N mice. These findings demonstrate that neu-N mice possess latent pools of high-avidity neu-specific CD8(+) T cells that can be recruited to produce an effective antitumor response if T reg cells are blocked or removed by using approaches such as administration of cyclophosphamide before vaccination.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ativação Linfocitária
/
Linfócitos T CD8-Positivos
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Epitopos de Linfócito T
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Vacinas Anticâncer
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Neoplasias Mamárias Experimentais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Exp Med
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Estados Unidos