Interferon-ε is a tumour suppressor and restricts ovarian cancer

Zoe R. C. Marks, Nicole K. Campbell, Niamh E. Mangan, Cassandra J. Vandenberg, Linden J. Gearing, Antony Y. Matthews, Jodee A. Gould, Michelle D. Tate, Georgie Wray-McCann, Le Ying, Sarah Rosli, Natasha Brockwell, Belinda S. Parker, San S. Lim, Maree Bilandzic, Elizabeth L. Christie, Andrew N. Stephens, Eveline Geus, Matthew J. Wakefield, Gwo-Yaw Ho, Orla McNally, Iain A. McNeish, David D. L. Bowtell, Nicole A. Weerd, Clare L. Scott, Nollaig M. Bourke and Paul J. Hertzog ()
Additional contact information
Zoe R. C. Marks: Hudson Institute of Medical Research
Nicole K. Campbell: Hudson Institute of Medical Research
Niamh E. Mangan: Hudson Institute of Medical Research
Cassandra J. Vandenberg: Walter and Eliza Hall Institute of Medical Research
Linden J. Gearing: Hudson Institute of Medical Research
Antony Y. Matthews: Hudson Institute of Medical Research
Jodee A. Gould: Hudson Institute of Medical Research
Michelle D. Tate: Hudson Institute of Medical Research
Georgie Wray-McCann: Hudson Institute of Medical Research
Le Ying: Hudson Institute of Medical Research
Sarah Rosli: Hudson Institute of Medical Research
Natasha Brockwell: Peter McCallum Cancer Centre
Belinda S. Parker: Peter McCallum Cancer Centre
San S. Lim: Hudson Institute of Medical Research
Maree Bilandzic: Monash University
Elizabeth L. Christie: Peter McCallum Cancer Centre
Andrew N. Stephens: Monash University
Eveline Geus: Hudson Institute of Medical Research
Matthew J. Wakefield: Walter and Eliza Hall Institute of Medical Research
Gwo-Yaw Ho: Walter and Eliza Hall Institute of Medical Research
Orla McNally: Peter McCallum Cancer Centre
Iain A. McNeish: Imperial College London
David D. L. Bowtell: Peter McCallum Cancer Centre
Nicole A. Weerd: Hudson Institute of Medical Research
Clare L. Scott: Walter and Eliza Hall Institute of Medical Research
Nollaig M. Bourke: Hudson Institute of Medical Research
Paul J. Hertzog: Hudson Institute of Medical Research

Nature, 2023, vol. 620, issue 7976, 1063-1070

Abstract: Abstract High-grade serous ovarian cancers have low survival rates because of their late presentation with extensive peritoneal metastases and frequent chemoresistance1, and require new treatments guided by novel insights into pathogenesis. Here we describe the intrinsic tumour-suppressive activities of interferon-ε (IFNε). IFNε is constitutively expressed in epithelial cells of the fallopian tube, the cell of origin of high-grade serous ovarian cancers, and is then lost during development of these tumours. We characterize its anti-tumour activity in several preclinical models: ovarian cancer patient-derived xenografts, orthotopic and disseminated syngeneic models, and tumour cell lines with or without mutations in Trp53 and Brca genes. We use manipulation of the IFNε receptor IFNAR1 in different cell compartments, differential exposure status to IFNε and global measures of IFN signalling to show that the mechanism of the anti-tumour activity of IFNε involves direct action on tumour cells and, crucially, activation of anti-tumour immunity. IFNε activated anti-tumour T and natural killer cells and prevented the accumulation and activation of myeloid-derived suppressor cells and regulatory T cells. Thus, we demonstrate that IFNε is an intrinsic tumour suppressor in the female reproductive tract whose activities in models of established and advanced ovarian cancer, distinct from other type I IFNs, are compelling indications of potential new therapeutic approaches for ovarian cancer.

Date: 2023
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-023-06421-w Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:620:y:2023:i:7976:d:10.1038_s41586-023-06421-w

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-023-06421-w

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().