A role for T-bet-mediated tumour immune surveillance in anti-IL-17A treatment of lung cancer.
Nat Commun
; 2: 600, 2011 Dec 20.
Article
en En
| MEDLINE
| ID: mdl-22186896
Lung cancer is the leading cause of cancer deaths worldwide. The cytokine interleukin-17A supports tumour vascularization and growth, however, its role in lung cancer is unknown. Here we show, in the lungs of patients with lung adenocarcinoma, an increase in interleukin-17A that is inversely correlated with the expression of T-bet and correlated with the T regulatory cell transcription factor Foxp3. Local targeting of interleukin-17A in experimental lung adenocarcinoma results in a reduction in tumour load, local expansion of interferon-γ-producing CD4(+) T cells and a reduction in lung CD4(+)CD25(+)Foxp3(+) regulatory T cells. T-bet((-/-)) mice have a significantly higher tumour load compared with wild-type mice. This is associated with the local upregulation of interleukin-23 and induction of interleukin-17A/interleukin-17R-expressing T cells infiltrating the tumour. Local anti-interleukin-17A antibody treatment partially improves the survival of T-bet((-/-)) mice. These results suggest that local anti-interleukin-17A antibody therapy could be considered for the treatment of lung tumours.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Adenocarcinoma
/
Regulación Neoplásica de la Expresión Génica
/
Proteínas de Dominio T Box
/
Factores de Transcripción Forkhead
/
Anticuerpos Neutralizantes
/
Pulmón
/
Neoplasias Pulmonares
Tipo de estudio:
Screening_studies
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
Reino Unido