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

作者：Reppert S; Boross I; Koslowski M; Tuereci O; Koch S; Lehr H A; Finotto S^*

来源：Nature Communications, 2011, 2(1): 600.

DOI：10.1038/ncomms1609

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-.-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-17Rexpressing 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.

• 出版日期2011-12