title: Pro-tumour activity of interleukin-22 in HPAFII human pancreatic cancer cells.
abstract: Interleukin (IL)-22 is a cytokine involved in inflammatory and wound healing processes that is secreted primarily by T helper type 17 (Th17) cells. IL-22 receptor (IL-22R) expression is limited to epithelial cells of the digestive organs, respiratory tract and skin. Most tumours originating in these sites over-express IL-22R. Interestingly, there is an increase in Th17 frequency within the peripheral blood and tumour microenvironment of advanced cancer patients. Subsequently, IL-17 has been shown to display both pro-tumour and anti-tumour functions. Because many tumours lack expression of the IL-17 receptor, the effects of IL-17 on tumour growth are generated by cells that surround the tumour cells. Like IL-17, high levels of IL-22 have been detected in tumour tissues and the peripheral blood of cancer patients; however, the direct effect of IL-22 on tumour cells has remained largely unknown. In this report, we show that IL-22 stimulated production of vascular endothelial growth factor (VEGF) and the anti-apoptotic factor Bcl-X(L) in IL-22R-positive HPAFII human pancreatic cancer cells. Additionally, IL-22 augmented HPAFII cell production of immunosuppressive cytokines. We show further that IL-22 activation of HPAFII cells diminished T cell production of interferon (IFN)-γ through the action of IL-10. Strikingly, we show for the first time that IL-22 can fully protect cancer cells from natural killer (NK) cell-mediated cytotoxicity by stimulating tumour production of IL-10 and transforming growth factor (TGF)-β1. Our data support the idea that IL-22 may act to promote the pathogenesis of cancers rather than function in anti-tumour immunity.
authors.affiliation: Department of Basic Sciences, Georgia Campus - Philadelphia College of Osteopathic Medicine, Suwanee, Georgia, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Curd
authors.forename: S E
authors.initials: SE
authors.lastname: Favors
authors.forename: R K
authors.initials: RK
authors.lastname: Gregg
mesh_terms: D017209:Apoptosis / Q000276:immunology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism* / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D009389:Neovascularization, Pathologic / Q000276:immunology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D007378:Interleukins; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22