Systemic injection of TLR1/2 agonist improves adoptive antigen-specific T cell therapy in glioma-bearing mice.
Clin Immunol
; 154(1): 26-36, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-24928324
ABSTRACT
Adoptive immunotherapy is an attractive strategy for glioma treatment. However, some obstacles still need be overcome. In this study, GL261-bearing mice treated with adoptively transferred antigen-specific T cells and systemic injection of bacterial lipoprotein (BLP), a TLR1/2 agonist, got a long-term survival and even immune protection. By analyzing adoptive T cells, it was found that BLP maintained T cell survival, proliferation and anti-tumor efficacy in the brains of tumor-bearing hosts. Moreover, tumor microenvironment was modified by up-regulating IFN-γ-secreting CD8+ T cells and down-regulating MDSC, which might be related with high CXCL10 and low CCL2 expression. In addition, TLR2 deficiency abrogated therapeutic effect with increased MDSC accumulation and decreased IFN-γ-secreting CD8+ T cells in the brains. Thus, the systemic injection of BLP could improve the adoptive T cell therapy by maintaining T cell persistence, modifying the tumor microenvironment and even inducing systemic anti-tumor immunity, which might offer a clinically promising immunotherapeutic strategy for glioma.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
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Imunoterapia Adotiva
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Linfócitos T CD8-Positivos
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Receptor 1 Toll-Like
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Receptor 2 Toll-Like
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Terapia Baseada em Transplante de Células e Tecidos
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Glioma
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article