Interleukin-27 Signaling Promotes Immunity against Endogenously Arising Murine Tumors |
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| Authors: | Karlo D. T. Natividad Simon R. Junankar Norhanani Mohd Redzwan Radhika Nair Rushika C. Wirasinha Cecile King Robert Brink Alexander Swarbrick Marcel Batten |
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| Affiliation: | 1. Immunological Diseases Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; 2. Cancer Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.; 3. St. Vincent''s Clinical School, University of New South Wales, Sydney, New South Wales, Australia.; University of Palermo, Italy, |
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| 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. |
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