Ovarian cancer is a heterogenous disease that is often managed with standard of care chemotherapy regimens, but greater than 70% of women with late-stage malignancy suffer from recurrent disease. Despite the successes of immune-based therapies in other cancers such as melanoma and non-small cell lung cancer, these therapies are poorly efficacious in ovarian cancer patients and single-agent therapy is unlikely to promote durable remissions. Our group and others have established that the immune system can attack ovarian tumors which delays disease progression, and in rare cases, provides complete regression in patients. Thus, there is an urgent need to understand the biological mechanisms that contribute to the ability of tumor cells to evade immune-mediated clearance. In this proposal, we will investigate how the induction of cellular-stress responses, often exhibited in tumors, contributes the sensitization of cancer cells to immune-mediated killing. Specifically, we will focus on how endoplasmic reticulum (ER) stress responses induce a shift in mRNA translation which lead to the production of peptides and proteins that have a potential to augment immune responses and the destruction of tumors. The potential of this study can be summarized by two key points: i) the elucidation of biological mechanisms responsible for the generation of immunogenic antigens will reveal a fundamental understanding of how tumors can be recognized and evade by the immune system, ii) the discovery of a new class of tumor antigens generated by cellular stress will catalyze the development of novel immune-based and vaccine-related therapeutics capable of providing effective treatments to a broad population of ovarian cancer patients.
My name is Dr. Patrick Innamarato. I earned my bachelor’s degree in Veterinary and Biomedical Sciences at The Pennsylvania State University in 2013. I then pursued and earned my PhD in Cancer Biology in 2020 at the University of South Florida in affiliation with the H. Lee Moffitt Cancer Center. My graduate studies in the Dr. Shari Pilon-Thomas laboratory focused on understanding the mechanisms of immunosuppression in melanoma patients that receive adoptive T cell therapies. Using mouse models and patient specimens, my research described how interactions between immunosuppressive myeloid cells restrains the anti-tumor activity of adoptively transferred T cells which is associated with poor patient outcomes in clinical trials conducted at the H. Lee Moffitt Cancer Center. Upon completing my PhD in the Pilon-Thomas laboratory, I accepted a position as a post-doctoral researcher in the Dr. Jose Conejo-Garcia laboratory. My current research is focused on demonstrating the immunogenicity of ovarian cancer. Specifically, my work is centered on describing mechanisms by which cellular stress regulates the expression of immunogenic targets in tumor cells. This research will elucidate how dominant antigens presented by ovarian tumor cells are regulated and lead to the recognition by T cells, providing a fundamental understanding of how spontaneous immune pressure within tumors can restrain malignant progression. This research will also reveal novel targets in tumor cells that can guide the development of novel immunotherapies for ovarian cancer and potentially other tumor types.