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Nat Commun. 2011 Dec 20;2:600. doi: 10.1038/ncomms1609.

A role for T-bet-mediated tumour immune surveillance in anti-IL-17A treatment of lung cancer.

Author information

1
Department of Anesthesia, Laboratories of Cellular and Molecular Lung Immunology, Institute of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Hartmannstraße 14, Erlangen 91052, Germany.

Abstract

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.

PMID:
22186896
DOI:
10.1038/ncomms1609
[Indexed for MEDLINE]

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