title: Increased expression of the Th17-IL-6R/pSTAT3/BATF/RorγT-axis in the tumoural region of adenocarcinoma as compared to squamous cell carcinoma of the lung.
abstract: Here we describe increased expression of IL6R in the tumoural region of lung tissue from patients affected by lung adenocarcinoma as compared to squamous cell lung carcinoma. Moreover, here we found increased IL6R in the tumour free part of the lung. By using a murine model of lung adenocarcinoma, we discovered that few lung tumour cells expressed IL-6R and CD4+CD25+Foxp-3+ T regulatory cells down-regulated IL-6R in the tumour bearing lungs. Downstream of IL-6R, the Th17 lineage-specification factors: Signal transducer and activator of transcription 3 (STAT3), Basic leucine zipper transcription factor, BATF and a protein encoded by the RORC in human (RAR-related orphan receptor C) (RORγT), were also found induced in the tumoural region of lung tissue from patients affected by lung adenocarcinoma as compared to those carrying squamous cell carcinoma. Moreover, pSTAT3 protein was found phosphorylated and auto-phosphorylated in the tumoural region of patients with adeno cell carcinoma of the lung as compared to the tumoural region of patients with squamous cell carcinoma of the lung. Intranasal application of anti-IL-6R antibodies in a murine model of lung adenocarcinoma, induced T regulatory cell markers such as Foxp3, Ctla4, Icos, Il10, Il21, Folr4 and Lag3 and inhibited Rorc in lung adenocarcinoma.
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Ljubov
authors.initials: L
authors.lastname: Balabko
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Katerina
authors.initials: K
authors.lastname: Andreev
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Burmann
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schubert
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Mathews
authors.affiliation: Department of Thoracic Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Denis I
authors.initials: DI
authors.lastname: Trufa
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Reppert
authors.affiliation: Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Rau
authors.affiliation: Department of Anatomy II, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schicht
authors.affiliation: Department of Thoracic Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Horia
authors.initials: H
authors.lastname: Sirbu
authors.affiliation: Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Department of Molecular Pneumology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany.
authors.forename: Susetta
authors.initials: S
authors.lastname: Finotto
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology*; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000276:immunology*; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C099359:BATF protein, human; D050976:Basic-Leucine Zipper Transcription Factors; C431772:Batf protein, mouse; C508603:IL6R protein, human; D009363:Neoplasm Proteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse