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A significant study has discovered the anti-tumour activities of the immune protein interferon epsilon, which in pre-clinical models blocks the metastasis of ovarian cancer cells by instructing immune cells to kill the cancer cells

The search for preventions and cures for the most prevalent and deadly form of ovarian cancer has now turned inward with the discovery of the anti-tumour activities of an immune protein called ‘interferon epsilon’. This research was published in the journal Nature and was co-led by Trinity College Dublin researcher Dr Nollaig Bourke.

Interferons (IFN) are a type of immune signalling protein, or cytokine, which can kill tumour cells and activate anti-tumour immune responses. Dr Nollaig Bourke, School of Medicine – who worked with colleagues in the Hudson Institute of Medical Researchin Melbourne, Australia, before returning to establish her own research immunology group at Trinity – explained: “Early in this study we found that women with high grade serous ovarian cancer no longer had the normal expression of an immune protein called interferon epsilon in their female reproductive tract.

“This was really interesting to us as we knew that interferon epsilon was part of a family of proteins known for their anti- tumour activities and we wondered what would happen if we could try and restore this lost expression – could giving interferon epsilon back help block the growth of ovarian cancer cells and therefore prevent the growth of primary and secondary tumours?”

A key motivation for the team is the poor survival rate for women with ovarian cancer, particularly high-grade serous ovarian carcinoma (HGSOC). Patients are often not diagnosed until later stages of the diseases when cancer cells have metastasised from the initial tumour to other sites in the body, making the disease really difficult to treat. About 400 women in Ireland are diagnosed with ovarian cancer each year.

A big advance in cancer treatment in recent years has been cancer immunotherapies, where the immune system is harnessed to kill cancer cells. The researchers received pilot funding from the US Defence Department’s Ovarian Cancer Research Programme to assess interferon epsilon as a novel immunotherapy in ovarian cancer.

Dr Bourke continued: “What was really striking about our study was that when we gave interferon epsilon in our pre- clinical models, it was able to directly kill tumour cells but more importantly, it was really good at instructing immune cells in the body to target and kill cancer cells involved in metastasis, thus blocking the development of secondary tumours.”

This study was made possible by the team of expert immunology scientists and oncology clinicians who collaborated to make these discoveries, including former Trinity alumni Dr Nicole Campbell and Dr Niamh Mangan. Dr Campbell, who joined the research team after completing a PhD in Trinity, is the publication’s joint first author and has been working for several years on understanding how these treatments which target the body’s immune system can be optimised to

improve its ability to fight the tumour. Dr Campbell said: “Cancer

immunotherapies have been very successful in the treatment of other types of cancer, but they have had limited success in ovarian cancer – we’re looking to change that.

“We know that in High Grade Serous Ovarian Cancers [the commonest form of ovarian cancer] tumour cells recruit and activate ‘immunosuppressive’ cells which prevent anti-tumour immune cells from killing tumour cells, so we’re aiming to develop new therapeutics which can reverse that process and improve survival rates.”

Professor Paul Hertzog, Centre For Innate Immunity & Infectious Diseases, Hudson Institute of Medical Research, who co-led the study with Dr Bourke, said: “We now know that Interferon epsilon is naturally made in the [epithelial] cells lining organs such as the female reproductive tract where we knew it acts as a natural booster of immunity to infections. Our recent discovery is that it also acts as a tumour suppressant, and that it is lost during the process of ovarian tumour formation.

“We know from pre-clinical models that administering it will dramatically inhibit ovarian cancer growth, particularly in cases where the cancer has metastasised into the peritoneal cavity.”

The next step is to understand which immune cells are important to the anti- tumour activity of IFN epsilon, and to test whether it is effective on human cells.

Combining studies in mice and using the byproducts of human ovarian cancer treatment, the team now aim to better understand how IFN epsilon works to protect against ovarian cancer and move a big step closer to ‘first-in-human’ clinical trials. The goal is to develop IFN epsilon as a new immunotherapy for ovarian cancer.