The immunosuppressive tumor microenvironment is a major barrier to the successful treatment of ovarian cancer. The main goal of our research is to develop therapeutic strategies to overcome this immunosuppression and improve patient responses to cancer immunotherapy. Tumor associated macrophages are a prominent feature of the tumor microenvironment. Traditionally macrophages are divided into two different polarization states referred to as M1 and M2. In this simplified model, M1 macrophages promote inflammation and mediate anti-tumor effects whereas M2 macrophages are immunosuppressive and pro-tumor. In recent years, an increased appreciation for the incredible heterogeneity of macrophages has indicated that tumor associated macrophages cannot simply be divided into M1 or M2 classifications. Rather, our goal is to use full spectral flow cytometry to characterize tumor associated macrophages based on 40 surface markers. This will allow us to capture the diversity of ovarian cancer associated macrophages to functionally define specific macrophage subsets for the first time. We will then be able to viably sort these subsets and determine their functional roles in vitro as well as in patient-matched patient-derived xenograft mouse models. The overall goal of our study is lay the foundation for future work developing macrophage-targeting therapies for use in combination with T cell based immunotherapies for the treatment of advanced metastatic ovarian cancer.
This grant was made possible in part by a generous donation from Ovarian Cycle Atlanta in honor of Bethany Diamond.
Dr. Joshua Eggold received his PhD in Cancer Biology from Stanford University, where he performed his thesis work in the laboratory of Dr. Erinn Rankin. His research focused on the role of polymorphonuclear myeloid-derived suppressor cells in ovarian cancer, as well as the use of FLASH radiation to treat ovarian cancer. He is currently a postdoctoral researcher at the University of Pennsylvania in the laboratory of Dr. Dan Powell Jr. In this position, he has continued to follow his passion for ovarian cancer research by studying the role of tumor-associated macrophages in ovarian cancer and the potential to therapeutically target them using CAR T cells.