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      1. Author :
        Reppert, S.; Boross, I.; Koslowski, M.; Tureci, O.; Koch, S.; Lehr, H. A.; Finotto, S.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Nat Commun
      6. Products :
      7. Volume :
        2
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        LL/2-luc-M38, LL/2-luc, Lewis Lung Carcinoma, IVIS, Adenocarcinoma/drug therapy/genetics/*immunology/metabolism/pathology; Administration, Intranasal; Adult; Aged; Animals; Antibodies, Neutralizing/administration & dosage/*therapeutic use; Antigens, CD/immunology; Female; Forkhead Transcription Factors/genetics/*immunology/metabolism; Gene Expression Regulation, Neoplastic/drug effects/*immunology; Humans; Immunologic Surveillance; Interferon-gamma/biosynthesis/immunology; Interleukin-17/immunology/metabolism; Interleukin-23/immunology/metabolism; Lung/drug effects/*immunology/metabolism/pathology; Lung Neoplasms/drug therapy/genetics/*immunology/metabolism/pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Middle Aged; T-Box Domain Proteins/deficiency/*genetics/immunology; T-Lymphocytes, Regulatory/immunology
      12. 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-gamma-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.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22186896
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10544