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

S. Reppert, I. Boross, M. Koslowski, Ö. Türeci, S. Koch, H.A. Lehr and S. Finotto ()
Additional contact information
S. Reppert: Laboratories of Cellular and Molecular Lung Immunology, Institute of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Hartmannstraße 14, Erlangen 91052, Germany.
I. Boross: Laboratory of Cellular and Molecular Lung Immunology, Institute of Molecular Medicine, Universitätsmedizin Mainz
M. Koslowski: Internal Medicine III, Universitätsmedizin Mainz
Ö. Türeci: Internal Medicine III, Universitätsmedizin Mainz
S. Koch: Laboratories of Cellular and Molecular Lung Immunology, Institute of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Hartmannstraße 14, Erlangen 91052, Germany.
H.A. Lehr: Institute of Pathology, Centre Hospitalier Universitaire Vaudois, University of Lausanne
S. Finotto: Laboratories of Cellular and Molecular Lung Immunology, Institute of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Hartmannstraße 14, Erlangen 91052, Germany.

Nature Communications, 2011, vol. 2, issue 1, 1-11

Abstract: 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.

Date: 2011
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DOI: 10.1038/ncomms1609

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