Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies.
Nat Med
; 15(5): 528-36, 2009 May.
Article
em En
| MEDLINE
| ID: mdl-19396174
ABSTRACT
Identifying key factors that enhance immune responses is crucial for manipulating immunity to tumors. We show that after a vaccine-induced immune response, adjuvant interleukin-7 (IL-7) improves antitumor responses and survival in an animal model. The improved immune response is associated with increased IL-6 production and augmented T helper type 17 cell differentiation. Furthermore, IL-7 modulates the expression of two ubiquitin ligases Casitas B-lineage lymphoma b (Cbl-b), a negative regulator of T cell activation, is repressed, and SMAD-specific E3 ubiquitin protein ligase-2 (Smurf2) is enhanced, which antagonizes transforming growth factor-beta signaling. Notably, we show that although short term IL-7 therapy potently enhances vaccine-mediated immunity, in the absence of vaccination it is inefficient in promoting antitumor immune responses, despite inducing homeostatic proliferation of T cells. The ability of adjuvant IL-7 to antagonize inhibitory networks at the cellular and molecular level has major implications for immunotherapy in the treatment of tumors.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interleucina-7
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Infecções por Arenaviridae
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Vacinas Anticâncer
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Imunoterapia
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Coriomeningite Linfocítica
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Vírus da Coriomeningite Linfocítica
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article