More than 14,000 patients in the United States die of ovarian cancer each year, making this cancer the fifth leading cause of cancer death among women in the United States. Within different subtypes of ovarian cancer, high-grade serous ovarian cancer (HGSC) is not only the most common type but also the deadliest. Inheritance of one defective copy of either of the two breast cancer susceptibility genes, BRCA1 and BRCA2, predisposes individuals to breast and ovarian cancers. Indeed, approximately 50% of HGSCs harbor genetic and epigenetic alterations in the BRCA1 and 2 genes, which are members of the DNA repair pathway. Interestingly, tumors that arise in BRCA carriers are likely to be more sensitive to platinum-based chemotherapy and are associated with improved survival, but the underlying mechanisms have not been well elucidated. In our preliminary studies, we discovered that BRCA-deficient tumors have increased levels of a protein named interferon induced transmembrane protein 3 (IFITM3), compared to BRCA-proficient tumors. Its altered expression has been linked to various pathologic and immune-related diseases including viral infections, inflammatory bowel disease, and cancer, but its role in the development of BRCA-deficient HGSC remains unknown. Recently, we found that high IFITM3 levels in BRCA-deficient HGSC cells correlated with higher expression of MHC I and II molecules that mediate improved immune response. Increased IFITM3 has also been shown to activate B cells and to increase B cell density which is usually associated with improved survival. Therefore, we hypothesize that increased DNA damage in BRCA-deficient HGSC cells upregulates IFITM3 expression which in turn activates T- and B-cells to kill the cancer cells. A deeper understanding of the mechanisms by which IFITM3 modulates the immune microenvironment in BRCA-deficient HGSC will provide us new treatment strategies based on up-regulating IFITM3 alone in both BRCA-deficient and -proficient HGSC, or in combination with other immune checkpoint inhibitors to improve their efficacies. Moreover, IFITM3 may also have the potential to become a novel biomarker to predict response to immunotherapies, and therefore patients can be stratified for treatment.
Dr. Sammy Ferri-Borgogno is currently a postdoctoral research fellow in the laboratory of Dr. Samuel Mok in the Department of Gynecologic Oncology and Reproductive Medicine at UT MD Anderson Cancer Center (MDACC), where she is devoted to elucidating immune landscapes and crosstalk signaling networks that interplay in the ovarian tumor microenvironment to modulate clinical outcomes.
Dr. Ferri-Borgogno earned a Bachelor of Science degree in Biotechnology and subsequently a Summa Cum Laude Master of Science degree in Medical Biotechnology from the University of Turin, Italy, where she characterized the role of alpha-enolase in pancreatic ductal adenocarcinoma. Dr. Ferri-Borgogno studied how cancer biology, -omics technologies and immunology might be integrated to understand host-tumor responses and identify new diagnostic markers and therapeutic targets for solid tumors under the guidance of Prof. Francesco Novelli during her doctoral training at the University of Turin, Italy. Her thesis work demonstrated the functional relevance of ENO1 inhibition in human cancer cell lines through proteomic, biochemical and functional approaches. Dr. Ferri-Borgogno started her postdoctoral training in the laboratory of Dr. Anirban Maitra at MDACC with the goal of develop and expand her passionate interest in cancer biology as well as explore a more translational research approach. Here she focused her attention on characterizing the pivotal role of two main epigenetic regulators in pancreatic cancer, ARID1A and MLL3.
Recently, her willing to explore new fields and to expand her research knowledge in cancer biology, made Dr. Ferri-Borgogno to join the laboratory of Dr. Samuel Mok. As a senior post-doctoral fellow in the lab she has primary responsibility for all research initiatives and projects related to clarify the molecular/cellular interactions existing between stromal cells and cancer immunity to identify markers in the ovarian tumor microenvironment that can simultaneously normalize aberrant angiogenesis and increase tumor immune cell activation and infiltration, thus resulting in significant treatment outcomes. To demonstrate her hard work in the field of ovarian cancer, and recognize her research excellence, Dr. Ferri-Borgogno was awarded the 2020 Diane Denson Tobola Fellowship in Ovarian Cancer Research at MD Anderson Cancer Center.
With the support of the Ovarian Cancer Research Alliance, Dr. Ferri-Borgogno will utilize cutting-edge technologies such as Spatial Transcriptomics (ST) and Imaging mass cytometry (IMC) to identify biomarkers and molecular mechanisms associated with chemoresistance in ovarian cancer.