2022 Mentored Investigator Grant Recipient — Erin Wesley, PhD
Erin Wesley, PhD
University of Minnesota Twin Cities
Impact of Cytomegalovirus and Inflammation on NK Cells in Ovarian Cancer
Project Summary
Current treatments for ovarian cancer are limited in providing prolonged disease free and overall survival outcomes. There is a critical need for novel therapeutic strategies to address these deficiencies. My research aims to identify how to improve patient survival by maximizing natural killer (NK) cell therapies in the treatment of ovarian cancer. Two complicating factors that I will focus on is the impact Cytomegalovirus (CMV) and inflammation has on the immune system and how they impact this disease. CMV is a highly prevalent herpesvirus that infects over 50% of the population. CMV is usually dormant, but can be reactivated due to inflammation or immune suppression. We recently published our findings that women with advanced stage ovarian cancer (OC) at the time of cytoreductive surgery had significantly better overall survival when they were found to have had evidence of prior CMV infection with low levels of inflammation (89 months) compared to patients that had a prior a CMV positive infection with high levels of inflammation (31 months). Recent studies have identified a subset of NK cells known as adaptive NK cells that expand in response to CMV, are long-lived and have enhanced killing, which, in other cancers, are thought to contribute to cancer control. We have data showing significantly increased numbers of adaptive NK cells in both the blood and ascites of women positive for CMV compared to CMV negative patient samples at the time of surgery These data support our hypothesis that CMV reactivation in the right setting may provide increased ability to fight ovarian cancer. We propose to define the role CMV and inflammation play in the survival of ovarian cancer patients by determining how these factors affect the evolution of adaptive NK cells. Our goal is to evaluate serum and ascites in 51 high grade serous ovarian cancer patients, previously collected at the time of surgery, for the presence of adaptive NK cells to determine if these cells are drivers for the changes we observed in survival. The central hypothesis is that CMV reactivation in the setting of low inflammation may improve patient survival by expanding a subset of adaptive NK cells that have an enhanced ability to kill ovarian cancer. Confirmation of the hypothesis will provide an innovative approach to manipulating the immune system with the goal of increasing survival for women with ovarian cancer. At the completion of this project, we will have gained insight into the impact CMV and inflammation have on adaptive NK cells and the immune response in ovarian cancer. Our findings are expected to have a significant impact on the treatment strategies for women with this disease and will provide insight into strategies such as anti-inflammatory or anti-viral agents that could be employed at the time of surgery or longitudinally to improve the survival of women living with ovarian cancer.
This grant was made possible in part by a generous donation from The Dorow Family, Kicking Cancer One Dance at a Time, in honor of Mary Lynn Dorow.
Bio
Dr. Erin Wesley is currently a postdoctoral fellow in Dr. Melissa Geller’s lab at the University of Minnesota. Dr. Wesley received her undergraduate degree in Biochemistry and Biotechnology from Minnesota State University of Moorhead. In 2018, she obtained her PhD from the Medical College of Wisconsin, under the supervision of Dr. Matthew Riese. Dr. Wesley’s graduate studies focused on targeting CD8 T cell signaling downstream of the T cell receptor to enhance anti-tumor responses. In 2019, she joined Dr. Melissa Geller’s laboratory as a postdoctoral fellow on the Hematology Research Training Program T32 at the University of Minnesota. In addition, Dr. Wesley is also actively pursuing a Master’s in Clinical Research at the University of Minnesota with an overall goal of improving ovarian cancer outcomes. Her research focuses on understanding the role of cytomegalovirus infection and inflammation on the immune system and how it influences the adaptive NK cell response in ovarian cancer.