Impact of Estrogen Signaling on Tumor Immunity and Response to Immune Therapy in Ovarian Cancer

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. The hormone estrogen impacts immune function in both healthy people and in cancer models. Estrogen receptors on tumor cells have been targeted for ovarian cancer treatment, but the impact of estrogen on immune cells in the ovarian tumor environment is not known. We sought to test whether selective agents targeting distinct estrogen signaling pathways can enhance the effects of immune therapy in ovarian cancer. Results to date indicate that estrogen signaling impacts both tumor cell and immune cell viability and function. Planned experiments in Year 2 will test whether these effects can enhance treatment with immune therapy in mice. Our goal is to identify a combination of estrogen signaling agents and immune checkpoint antibodies that optimally induce an immune response against ovarian cancer.