title: Interleukin-27 signaling promotes immunity against endogenously arising murine tumors.
abstract: Interleukin-27 (IL-27) is a pleiotropic cytokine but its immunosuppressive effects predominate during many in vivo immunological challenges. Despite this, evidence from tumor cell line transfer models suggested that IL-27 could promote immune responses in the tumor context. However, the role of IL-27 in immunity against tumors that develop in situ and in tumor immunosurveillance remain undefined. In this study, we demonstrate that tumor development and growth are accelerated in IL-27 receptor α (Il27ra)-deficient mice. Enhanced tumor growth in both carcinogen-induced fibrosarcoma and oncogene-driven mammary carcinoma was associated with decreased interferon-γ production by CD4 and CD8 T cells and increased numbers of regulatory T-cells (Treg). This is the first study to show that IL-27 promotes protective immune responses against endogenous tumors, which is critical as the basis for future development of an IL-27 based therapeutic agent.
authors.affiliation: Immunological Diseases Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: Karlo D T
authors.initials: KD
authors.lastname: Natividad
authors.forename: Simon R
authors.initials: SR
authors.lastname: Junankar
authors.forename: Norhanani
authors.initials: N
authors.lastname: Mohd Redzwan
authors.forename: Radhika
authors.initials: R
authors.lastname: Nair
authors.forename: Rushika C
authors.initials: RC
authors.lastname: Wirasinha
authors.forename: Cecile
authors.initials: C
authors.lastname: King
authors.forename: Robert
authors.initials: R
authors.lastname: Brink
authors.forename: Alexander
authors.initials: A
authors.lastname: Swarbrick
authors.forename: Marcel
authors.initials: M
authors.lastname: Batten
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology*; D018123:Receptors, Interleukin; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; D007378:Interleukins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D007371:Interferon-gamma
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