Abstract PR-15: Neuroimmune dysregulation in ovarian cancer: the role of chronic stress on microglial activation and systemic inflammation

Abstract Patients with ovarian cancer (OC) often experience depression, which negatively impacts their quality of life and prognosis. Our research indicates that chronic stress (CS) induces systemic inflammation, contributing to disease progression. Other studies have also underscored its role in developing depressive symptoms. Microglia, the brain’s resident immune cells, are key regulators of neuroinflammation and can profoundly influence neural circuit function under stress. However, the effects of CS and OC on depressive symptoms in OC patients remain poorly understood. This study aims to investigate whether CS and OC lead to changes in the hippocampus (HPC) that result in depressive-like behavior in mice with OC, hypothesizing that CS will enhance tumor-related microglial inflammation and impair neuronal health in the HPC. In these studies, we inoculated C57BL/6 mice with IG10luc or ID8luc cells and subjected them to daily restraint stress for four weeks. Brains were processed for immunofluorescence analysis of IBA1, BDNF, IL1β, claudin-5, CD31, and albumin. Our results show that CS accelerated tumor growth, increased microglial infiltration (IBA1+ cells), elevated IL-1β levels, and reduced neuronal health (as indicated by BDNF) in the HPC. BBB integrity was compromised, as evidenced by reduced claudin-5 coverage of blood vessels (CD31) and increased albumin in the HPC of stressed mice. Milliplex analysis of serum cytokines showed that stressed mice had elevated circulating levels of IL1β and TNFα, indicating a heightened systemic inflammatory state in both syngeneic mouse models. In vitro experiments using stress hormones demonstrated upregulation of NFκB pathway-related proteins in microglia, highlighting the significant role of the central inflammatory pathway in microglial activation. These findings suggest that CS and OC drive neuroinflammation and BBB disruption, which may underlie the development of depressive symptoms. This study lays the groundwork for future research into how OC and CS can affect brain activity and behavior. Citation Format: Luinet L. Melendez-Rodriguez, Luis M. Rivera-Perez, Nemesis J. Torres-Rivera, Yadiel A. Rivera-Lopez, Alanis P. Torres-Rosado, Jaydiel A. Casiano-Martinez, Raian Imad-Hamad, Melanie Ortiz-Leon, Zuliann S. Galarza-Ruiz, Orlando I. Torres-Rodriguez, Guillermo N. Armaiz-Pena. Neuroimmune dysregulation in ovarian cancer: the role of chronic stress on microglial activation and systemic inflammation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Mechanisms of Cancer Immunity and Cancer-related Autoimmunity; 2025 Sep 24-27; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(9 Suppl):Abstract nr PR-15.