High-grade serous ovarian cancers have low survival rates because of their late presentation with extensive peritoneal metastases and frequent chemoresistance, 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.
Department of Gynaecologic Oncology, Center for Gynaecologic Oncology Amsterdam, Cancer Center Amsterdam, Amsterdam University Medical Centres, Amsterdam, Netherlands.
Ovarian-adnexal lesions are conventionally assessed with ultrasound (US) under the guidance of the Ovarian-Adnexal Reporting and Data System (O-RADS). However, the low specificity of O-RADS results in many unnecessary surgeries. Here, we use co-registered US and photoacoustic tomography (PAT) to improve the diagnostic accuracy of O-RADS.
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Long Island Jewish Medical Center, Zucker School of Medicine at Hofstra/Northwell, Northwell Health, New Hyde Park, NY, United States.
The use of immunohistochemistry (IHC) and molecular pathology has been widely adopted over the past 3 decades and has aided in the precision of diagnosing gynecologic tumors. While many tumors can be diagnosed by histologic appearance on routine hematoxylin and eosin stained slides, the use of IHC has dramatically changed practice, leading to a better understanding and subtyping of gynecologic tumors. This detailed classification of tumors has aided in the implementation and development of targeted therapies.
Zinc is an essential trace element in the human body, playing a crucial role in cellular metabolism.Dysregulation of zinc homeostasis can lead to abnormal cellular metabolism, contributing to diseases and closely related to tumor development. Adequate zinc intake can maintain zinc homeostasis in the body and support normal cellular metabolism.
