Member Profile

Epithelial ovarian cancer (EOC) remains the most lethal gynecological malignancy in the United States. Implementing immunotherapeutic approaches to treat this disease holds promise, as the ovarian cancer microenvironment is immunologically active; both T cell and B cell infiltration are associated with prolonged patient survival (Zhang*, Conejo-Garcia* et al. N Engl J Med, 2003; Biswas et al. Nature, 2020). However, the microenvironment of ovarian cancer supports unique mechanisms which dampen productive antitumor immunity. This immunosuppressive environment likely explains the typically poor responses to current cancer immunotherapies, and ultimately leads to lethal malignant progression. Thus, the overarching vision of our laboratory is to 1) identify novel immunosuppressive mechanisms in ovarian cancer, and 2) to leverage this knowledge to rationally design the next generation of cancer immunotherapeutics. This builds upon previous work, in association within Dr. Jose Conejo-Garcia, where we elucidated the mechanism of epigenetic regulation of the immune checkpoint molecule, PD-1, in tumor-infiltrating T cells (Stephens*, Payne* et al. Immunity, 2017). We have also recently characterized the immune regulatory molecule, butyrophilin 3A1 (Payne et al. Science, 2020), which was found to dynamically suppress  T cells through an N-glycan-mediated mechanism involving CD45 in ovarian cancer beds. Current investigations in the lab are focused on identifying novel cellular stress response pathways intrinsic to both tumor cells and immune cells in order to understand how these responses perturb protective antitumor immunity. To pursue these studies, we utilize unique genetically engineered mouse models, CRISPR/Cas9 screening techniques and targeted gene ablation, transcriptomic, proteomic, and metabolomics-based approaches, as well as clinical specimens and collaborative efforts.