2022 Mentored Investigator Grant Recipient — Patrick Innamarato, PhD
Project Summary
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.