Interferon epsilon alters peritoneal myeloid cell populations in a murine model of ovarian cancer Nicole K. Campbell, Zoe R.C. Marks & Paul J. Hertzog Centre for Innate Immunity and Infectious Diseases, Hudson Institute of Medical Research, Clayton, VIC, Australia. The novel type I interferon, interferon epsilon (IFNε), is a unique cytokine which is constitutively expressed by epithelial cells under hormonal regulation in the female reproductive tract (FRT)1. Although IFNε is known to be protective against FRT infections 2, its role in the anti-cancer immune response remains unknown. Ovarian cancer is a common yet lethal FRT cancer, which metastasises to the peritoneal cavity in the majority of cases. Preliminary research has suggested that IFNε may protect against metastasis of ovarian cancer through action on both tumour and immune cells. Here, we have investigated the activity of IFNε in an orthotopic mouse model of ovarian cancer, using the ID8 tumour cell model. IFNε treatment was found to significantly reduce tumour burden, ascites development and peritoneal hemorrhaging in challenged mice, compared to both IFNβ and vehicle control (PBS). This was accompanied by stark differences in peritoneal immune cell populations; IFNε treatment increased numbers of resident large peritoneal macrophages, and reduced infiltration of pro-inflammatory small peritoneal macrophages. Furthermore, while a population of myeloid derived suppressor cells (MDSC) was observed in tumour-bearing mice, these MDSC were absent in mice which received IFNε treatment. These results indicate that modulation of myeloid cell populations in the peritoneal cavity may contribute to the efficacy of IFNε in preventing peritoneal metastasis of ovarian cancer. Further investigation into the immunomodulatory activity of IFNε within the peritoneal cavity is required to elucidate the potential of IFNε to be used to treat ovarian cancer and other peritoneal pathologies. 1. Marks, Z. R. C. et al. PROPERTIES AND FUNCTIONS OF THE NOVEL TYPE I INTERFERON EPSILON. Semin. Immunol. 43, 101328 (2019). 2. Fung, K. Y. et al. Interferon-ε protects the female reproductive tract from viral and bacterial infection. Science (80-. ). 339, 1088–1092 (2013).