title: A role for T-bet-mediated tumour immune surveillance in anti-IL-17A treatment of lung cancer.
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.
authors.affiliation: Department of Anesthesia, Laboratories of Cellular and Molecular Lung Immunology, Institute of Molecular Pneumology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Hartmannstraße 14, Erlangen 91052, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Reppert
authors.forename: I
authors.initials: I
authors.lastname: Boross
authors.forename: M
authors.initials: M
authors.lastname: Koslowski
authors.forename: Ö
authors.initials: Ö
authors.lastname: Türeci
authors.forename: S
authors.initials: S
authors.lastname: Koch
authors.forename: H A
authors.initials: HA
authors.lastname: Lehr
authors.forename: S
authors.initials: S
authors.lastname: Finotto
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000281:Administration, Intranasal; D000328:Adult; D000368:Aged; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007157:Immunologic Surveillance; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D053759:Interleukin-23 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D020825:T-Box Domain Proteins / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D057134:Antibodies, Neutralizing; D015703:Antigens, CD; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma