Gemcitabine depletes regulatory T-cells in human and mice and enhances triggering of vaccine-specific cytotoxic T-cells.
Int J Cancer
; 129(4): 832-8, 2011 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-21710545
ABSTRACT
Particle-mediated epidermal delivery (PMED) is a potent genetic vaccination method. However, a recent report found PMED only poorly and infrequently triggered antigen-specific cytotoxic T-cells in cancer patients. Here, we show that injection of the chemotherapeutic drug Gemcitabine in mice results in improvement of the efficacy of subsequent PMED vaccination against NY-ESO-1. We found in mice and in cancer patients that administration of Gemcitabine induces a transient reduction in the percentage of regulatory T-cells among CD4-positive cells. The higher relative sensitivity of regulatory T-cells compared to other CD4-positive T-cells toward cytostatic drugs can be linked to the higher frequency of proliferating cells in the regulatory compartment compared to the nonregulatory CD4-compartment in healthy people and cancer patients. Thus, by affecting regulatory T-cells more than other lymphocyte subsets, chemotherapeutic agents can create a transient hyperimmunoreactive window. Such a window would provide an ideal timepoint to administer a vaccine expected to induce a therapeutically relevant anticancer cytotoxic T-cell response.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T Citotóxicos
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Linfócitos T CD4-Positivos
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Linfócitos T Reguladores
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Vacinas Anticâncer
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Desoxicitidina
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Neoplasias
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Int J Cancer
Ano de publicação:
2011
Tipo de documento:
Article