Abstract LB073: Characterizing the ovarian cancer immune microenvironment in a syngeneic murine model

Abstract

Ovarian cancer (OvCa) is the deadliest gynecologic malignancy and, unfortunately, there are no effective salvage therapies for patients with refractory or resistant (r/r) disease. This is due in part to a limited understanding of the tumor microenvironment (TME), the marked differences between tumors established in different metastatic niches, and how the TME may change in the context of therapy resistance. OvCa uniquely metastasizes through peritoneal spread, resulting in various tumor niches with distinct tumor mutational burdens within the same patient. These niches have not been well characterized in murine models of OvCa and contribute to continued ineffective therapeutic interventions for r/r OvCa. To better define the ovarian cancer TME, we are utilizing orthotopic syngeneic murine models sensitive and resistant to the FDA approved PARP inhibitor (PARPi), Olaparib, ID8 and ID8-OR respectively. This model has both a TP53 and BRCA2 deletion, recapitulating the mutational status of OvCa patients likely to receive a PARPi. After tumor establishment, ascites as well as solid tumors at distinct tumor sites were collected and dissociated for further analysis. Using flow cytometric assays, we characterized the T cell infiltrate within the TME at distinct niches and surface marker expression on the tumor cells. These data confirm the presence of tumor infiltrating T cells within the OvCa TME across different tumor niches. We observed that the tumor infiltrating T cell percentage as well as their phenotype varies across the different metastatic niches of this disease. We observe a greater percentage of T cells present in the ascites as compared to the other metastatic sites including the omentum, the ovaries, and the bowel wall. Additionally, we observe a greater percentage of T-regulatory cells in PARPi-resistant omental tumors. Interestingly, while we do observe CD4+ and CD8+ T cells in the collected tumors, we do not see consistent expression of markers associated with either activation or exhaustion. Further studies are required to better characterize the functionality of the tumor infiltrating T cells. The data generated from these studies will inform the development of successful salvage immunotherapies for relapsed and refractory patients with ovarian cancer. Citation Format: Alexandra N. McMellen, Benjamin G. Bitler, Michael S. Leibowitz. Characterizing the ovarian cancer immune microenvironment in a syngeneic murine model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited s); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2): nr LB073.