Poster Presentation Melbourne Immunotherapy Spring Symposium 2025

30-Parameter Flow Cytometry Panels for Immunophenotyping Murine Models of High-Grade Serous Ovarian Cancer (#101)

Jasmine Chuah 1 , Nicole Campbell 1
  1. Hudson Institute of Medical Research, Oakleigh South, VIC, Australia

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 pathogens via the modulation of local, mucosal immune responses2. Given that several FRT pathologies including cancer, endometriosis, and infection can extend detrimentally into the peritoneal cavity, and are characterised by dysregulated immune responses, it is hypothesised that IFNε may prove protective against these pathologies via immunoregulatory effects that influence the phenotype, activity and composition of peritoneal immune cells.

High-grade serous ovarian cancer (HGSOC) is the most common subtype seen amongst ovarian cancer patients and represents almost 90% of diagnosed cases. It carries a 5-year survival rate of less than 40%, with many patients presenting with extensive peritoneal metastases and malignant ascites at time of diagnosis. Given the need for a treatment capable of modulating the development and pathogenesis of HGSOC, IFNε has been investigated, and subsequently, shown potential as a potent tumour suppressor for HGSOC3.

Previous data has heavily implied that IFNε achieves anti-tumour efficacy via immunomodulatory mechanisms3, however, the individual and collective peritoneal immune cell responses are not yet well-defined. With insight gleaned from single-cell RNA-sequencing of peritoneal immune cells following intraperitoneal administration of exogenous IFNε in the i.p. ID8Trp53-/-BRCA2-/- mouse model of HGSOC, we have developed 2 30-colour flow cytometry panels with the aim of characterising the key immune responses of peritoneal myeloid and lymphoid immune cells to IFNε in the context of HGSOC metastasis. These panels provide insight into IFNε’s mechanism of action, and further explore its potential as a future immunotherapy for peritoneal pathologies that induce aberrant activity in the peritoneal immune cells, primarily HGSOC metastases.

  1. Ka Yee Fung et al. ,Interferon-ε Protects the Female Reproductive Tract from Viral and Bacterial Infection.Science339,1088-1092(2013).DOI:10.1126/science.1233321
  2. Stifter, S. A. et al. Defining the distinct, intrinsic properties of the novel type I interferon, IFNϵ. J. Biol. Chem. 293, 3168–3179 (2018).
  3. Marks, Z.R.C., Campbell, N.K., Mangan, N.E. et al. Interferon-ε is a tumour suppressor and restricts ovarian cancer. Nature 620, 1063–1070 (2023). https://doi.org/10.1038/s41586-023-06421-w