Interleukin-15 rescues tolerant CD8+ T cells for use in adoptive immunotherapy of established tumors.
Nat Med
; 12(3): 335-41, 2006 Mar.
Article
em En
| MEDLINE
| ID: mdl-16474399
ABSTRACT
CD8+ T cells can mediate eradication of established tumors, and strategies to amplify tumor-reactive T-cell numbers by immunization or ex vivo expansion followed by adoptive transfer are currently being explored in individuals with cancer. Generating effective CD8+ T cell-mediated responses to tumors is often impeded by T-cell tolerance to relevant tumor antigens, as most of these antigens are also expressed in normal tissues. We examined whether such tolerant T cells could be rescued and functionally restored for use in therapy of established tumors. We used a transgenic T-cell receptor (TCR) mouse model in which peripheral CD8+ T cells specific for a candidate tumor antigen also expressed in liver are tolerant, failing to proliferate or secrete interleukin (IL)-2 in response to antigen. Molecular and cellular analysis showed that these tolerant T cells expressed the IL-15 receptor alpha chain, and could be induced to proliferate in vitro in response to exogenous IL-15. Such proliferation abrogated tolerance and the rescued cells became effective in treating leukemia. Therefore, high-affinity CD8+ T cells are not necessarily deleted by encounter with self-antigen in the periphery, and can potentially be rescued and expanded for use in tumor immunotherapy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunoterapia Adotiva
/
Linfócitos T CD8-Positivos
/
Interleucina-15
/
Tolerância Imunológica
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos