The novel type I interferon, interferon epsilon (IFNe), is a unique cytokine which is constitutively expressed under hormonal regulation in the female reproductive tract. Although IFNe has been identified as protective against sexually-transmitted infections1, its role in the anti-cancer immune response remains unknown. Ovarian cancer is a common yet lethal gynaecological cancer, which metastasises to the peritoneal cavity in the majority of cases. Preliminary research has suggested that IFNe may protect against ovarian cancer metastasis through its activity in both tumour and immune cells.
Here, we have investigated the activity of IFNe in an orthotopic murine model of ovarian cancer, using ID8 tumour cells with deletions in p53 and BRCA2, two of the most commonly mutated genes in human ovarian cancer cases. Immunophenotyping of peritoneal immune cells was performed by flow cytometry to detect changes in the composition and activation of lymphoid and myeloid cell populations. IFNe treatment was found to significantly reduce tumour burden in challenged mice, compared to both interferon beta and vehicle control. This was accompanied by stark differences in the populations of peritoneal immune cells; increased expression of the activation markers CD69 and PD1 was observed in both CD4+ and CD8+ T cells in IFNe treated mice, while IFNe also increased numbers of resident large peritoneal macrophages (LPM), and reduced infiltration of pro-inflammatory small peritoneal macrophages (SPM). These results indicate that modulation of peritoneal immune cells may contribute to the efficacy of IFNe in preventing peritoneal metastasis of ovarian cancer. In conclusion, this study supports further investigation into the immunomodulatory activity of IFNe within the peritoneal cavity, and the potential of IFNe to be used to treat ovarian cancer and other peritoneal pathologies.