The novel type I interferon, interferon epsilon (IFNε) possesses a unique manner of spatiotemporal expression and regulation1. Largely studied in the female reproductive tract (FRT), it has been shown to maintain homeostatic conditions and mediate protective immunity against common FRT pathogens1. Many FRT pathologies including cancer, endometriosis, and infection can extend detrimentally into the peritoneal cavity, and are characterised by dysregulated immune responses. Therefore, it is hypothesised that IFNε may have protective immunoregulatory effects that influence the phenotype, activity and composition of peritoneal immune cells under both steady state and inflammatory conditions.
Previous research utilizing syngeneic mouse models of high grade serous ovarian cancer (HGSOC) has indicated that IFNε administration alleviates tumour burden and ascites development, accompanied by changes in the frequencies and activity of peritoneal immune cell populations2. Following these observations, the peritoneal immune cells present in female wild-type (WT) and Ifnε-/- mice inoculated with ID8Trp53-/-BRCA2-/- tumour cells were investigated via immunophenotyping to determine the role of endogenous IFNε. The results indicated that endogenous IFNε may play a greater role in suppressing primary tumour growth and development, as the disseminated, intraperitoneal (i.p.) model of HGSOC in Ifnε-/- mice had similar tumour burden to the WT mice despite the absence of local IFNε in the peritoneal cavity.
Single-cell RNA-sequencing performed on the peritoneal cells following i.p. administration of exogenous IFNε further indicated that myeloid cells display the strongest interferon-regulated gene (IRG) response to IFNε, alongside CD8+ T cells. Through cell-depletion and cell-specific gene deletion systems in the i.p. ID8 mouse model of HGSOC, the contribution of IFNε signalling in myeloid cells, and activity by CD8+ T cells can be determined. These findings will provide insight into IFNε’s mechanism of action, and further explore its potential as a future immunotherapy for HGSOC patients.