Impact of Estrogen Signaling on Tumor Immunity and Response to Immune Therapy in Ovarian Cancer
Abstract
Immune therapy has been a major breakthrough in cancer treatment; however, the benefit for women with ovarian cancer has been limited. Our prior work demonstrated that modifying conditions in the tumor environment can significantly improve treatment with immune therapy in ovarian cancer models. Identifying new strategies to modify the tumor environment is expected to allow women with ovarian cancer to optimally benefit from immune therapy. Estrogen, a hormone produced by the ovaries and stored in fatty tissue, has been shown to impact immune function in both healthy people and in cancer models. Estrogen receptors on tumor cells have been targeted with hormonal treatment for ovarian cancer, but the impact of estrogen on immune cells in the ovarian tumor environment is not known. Our collaborator, Dr. Eric Prossnitz, discovered a novel estrogen receptor called GPER (G-protein estrogen receptor) that is expressed by immune cells. His work indicates that GPER regulates the treatment effects of immune checkpoint antibodies. Dr. Prossnitz has also developed drugs that can selectively target this receptor. Though our collaboration with Dr. Prossnitz, we have a unique opportunity to test whether GPER agents can enhance the effects of immune checkpoint antibodies for the treatment of ovarian cancer. The new GPER agents that Dr. Prossnitz has developed have been formulated for human administration. As a result, we expect that the results of these studies could be used to develop a clinical trial in the next 2-4 years. Our primary goal is to optimize the benefit of immune therapy through innovative combination regimens and to make these treatments available to patients. An exploratory goal of this work is to examine how estrogen effects in the tumor microenvironment impacts the interpretation of preclinical studies of novel therapies. Although most women with ovarian cancer have their ovaries removed as part of their initial surgical treatment, preclinical studies testing novel cancer treatments use reproductive-aged mice with intact ovarian function. In our studies, we will surgically remove the ovaries from mice before testing the effects of GPER agents on tumor immunity. As a result, our cancer models will more accurately reflect conditions in tumors of patients. If we demonstrate that estrogen levels can significantly impact the immune response to cancer, this would emphasize the importance of making sure that preclinical studies are conducted in models that recreate conditions in patients.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110337
Entities
People
- Sarah Adams
Organizations
- Health Sciences Center, University of New Mexico
- United States Army