P063 Interleukin-27 signaling promotes immunity against endogenously arising tumors

Abstract

Interleukin-27 (IL-27) is a pleiotropic cytokine but it’s 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 remains undefined. In this study, we use IL-27 receptor a (Il27ra) -deficient mice to examine the effect of physiological IL-27 in the context of anti-tumor responses. Carcinogen-induced fibrosarcoma and polyoma middle T antigen oncogene-driven mammary carcinomas are used as autochtonous tumor models. Associated changes in the immune response were examined by histology and flow cytometry. In this study, we demonstrate that tumor development and growth are accelerated in IL-27 receptor a (Il27ra) -deficient mice, using models of carcinogen-induced fibrosarcoma and polyoma middle T antigen oncogene-driven mammary carcinomas. Enhanced tumor growth was associated with decreased interferon-g production and increased number of regulatory T-cells (T reg ). 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.