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Using the immune system to stop ovarian cancer

Using the immune system to stop ovarian cancer
Suppression of epithelial IFNε in HGSOC and anti-tumor properties. a,b, IHC staining of human FT from two healthy women using rabbit anti-human IFNε (main image) or IgG control (inset), with haematoxylin counterstain (scale bars: 100 µm (a), 10 µm (b)). Images are representative of n = 20 individuals. c, Immunofluorescence staining of C57BL/6J mouse FT using anti-mouse IFNε (main image) or IgG control (inset), with DAPI counterstain. Image representative of n = 3 mice. Scale bar, 100 µm. d, mRNA expression of IFN genes in human FT epithelium (RNA-seq data derived from Australian Ovarian Cancer Study control samples1). CPM, counts per million. e, Quantification of IHC staining for IFNε in control human FT epithelium (n = 20), LGSOC (n = 6), HGSOC (n = 30) and ungraded serous samples (n = 28). Data are mean intensity scores for each sample stained in technical duplicates on tissue microarrays. Individual Mann–Whitney U tests compared to healthy FT control tissue. f, IFNε transcript expression plotted as normalized expression (from RNA-seq analysis) of IFNε in Australian Ovarian Cancer Study samples (n = 83 HGSOC samples, n = 7 FT epithelium). Median expression in tumor samples is indicated by the dotted line. g,h, A syngeneic orthotopic model of ovarian cancer in wild-type (WT) and Ifne−/− mice (Methods). g, The total number of metastatic deposits in the peritoneal cavity at endpoint. Data are mean ± s.d. of individual data points, n = 8 wild-type and n = 7 Ifne−/− mice. Unpaired two-tailed t-test. h, Total numbers of specific immune cell populations detected in peritoneal lavage fluid. Data are mean of cell counts measured for each genotype in a stacked bar graph. NK, natural killer. Two-way ANOVA. ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05. Credit: Nature (2023). DOI: 10.1038/s41586-023-06421-w

The search for preventions and cures has turned inward—focusing on the immune system to stop ovarian cancer.

Professor Paul Hertzog's research group at Hudson Institute of Medical Research has been working to expand on their discovery of a naturally occurring signaling protein found in the , Interferon (IFN-e), and its potential application in treatment of .

Their work involves harnessing the body's own system of signaling proteins to fight ovarian , with their latest research now published in Nature.

"Last year more than 1,000 Australians died of ovarian cancer, and the likelihood of living more than five years with the disease is still less than 50%," Professor Hertzog said. "It is often diagnosed late, and the most common treatments have limited effectiveness, with resistance to chemotherapy a major factor. It is a disease where new insights were needed"

This project built on the Hertzog research group's expertise in the study of IFNε and formed the Ph.D. project of Dr. Zoe Marks, which established that IFN-e protects against ovarian cancer via cells as well as the body's .

The publication's joint first author, Dr. Nicole Campbell, has been working for several years on understanding how these treatments which target the body's immune system can be optimized to improve its ability to fight the tumor.

"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," Dr. Campbell said.

"We know that in High Grade Serous Ovarian Cancers (the commonest form of ovarian cancer) tumor cells recruit and activate 'immunosuppressive' cells which prevent anti-tumor immune cells from killing , so we're aiming to develop new therapeutics which can reverse that process and improve survival rates."

This work was co-supervised by a post-doctoral scientist Dr. Nollaig Bourke, who has now returned to establish her own research group in Trinity College Dublin.

Dr. Bourke says that early in this study they found that women with High Grade Serous Ovarian Cancer no longer had the normal expression of interferon epsilon.

"This was really interesting to us as we knew that interferon epsilon was part of a family of proteins known for their anti-tumor activities and we wondered what would happen if we could try restore this lost expression," Dr. Bourke said.

Ovarian cancer tumor suppressor

Could giving interferon epsilon back help block the growth of ovarian cancer cells and therefore prevent the growth of primary and secondary tumors?

"The results that we got were very striking and confirmed that epsilon was a very effective tumor suppressor in ovarian cancer."

Prof Hertzog explained that since his laboratory's discovery of Interferon epsilon in 2004, a great deal of progress has been made, with Hudson Institute leading the world.

"At Hudson Institute we are now able to produce pure IFN-e, which allows us to conduct incredibly valuable research into how and where it can be used most effectively," he said.

Tumor suppressor lost during ovarian cancer formation

"We now know that Interferon epsilon is naturally made in the epithelium lining organs such as the female reproductive tract where it acts as a natural booster of immunity to infections. Our recent discovery is that it also acts as a tumor suppressant, and that it is lost during the process of ovarian tumor formation.

"We know from pre-clinical models that administering it will dramatically inhibit ovarian cancer growth, particularly in cases where the cancer has metastasized into the ," Prof Hertzog said.

More information: Paul Hertzog, Interferon-ε is a tumour suppressor and restricts ovarian cancer, Nature (2023). DOI: 10.1038/s41586-023-06421-w.

Journal information: Nature
Citation: Using the immune system to stop ovarian cancer (2023, August 16) retrieved 22 May 2024 from
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