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.
Highlights
Tumor immunosurveillance and anti-tumor immune responses are appreciated to be an important mechanism for protection against the emergence and growth of tumors
Our data demonstrate that IL-27 signaling enhances the antitumor immune response during in vivo development and growth of two diverse tumor types
MCA-induced fibrosarcoma and PyMTdriven mammary carcinoma development are accelerated in IL-27 receptor a (Il27ra)-deficient mice and are accompanied by reduced IFN-c production and increased percentages of Treg cells
Summary
Tumor immunosurveillance and anti-tumor immune responses are appreciated to be an important mechanism for protection against the emergence and growth of tumors. The importance of immune mediated protection against cancer is demonstrated by the enhanced rates of tumor initiation and growth in immune compromised patients and mice [1]. A T helper Type 1 (TH1) response, with accompanying IFN-c production and cytotoxic T and NK cell activation, is associated with effective anti-tumor immune activity while TH2 and TH17 responses are pro-tumorigenic [2]. Regulatory T cells (Treg) actively inhibit anti-tumor responses and high levels of Treg cells in patients correlate with poor prognosis in multiple cancer types [3,4]. Therapeutics that enhance TH1 responses or inhibit Treg cell activity are actively being sought for cancer treatment
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