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

Author

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  • 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.)

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.

Suggested Citation

  • S. Reppert & I. Boross & M. Koslowski & Ö. Türeci & S. Koch & H.A. Lehr & S. Finotto, 2011. "A role for T-bet-mediated tumour immune surveillance in anti-IL-17A treatment of lung cancer," Nature Communications, Nature, vol. 2(1), pages 1-11, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1609
    DOI: 10.1038/ncomms1609
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