Abstract A034: Spatial dynamics of vaccine-induced immunity in ovarian cancer: The central role of omental milky spots

Abstract Ovarian cancer is marked by rapid peritoneal dissemination and high mortality in advanced stages. Recent preclinical studies using humanized mouse models have demonstrated that mice therapeutically treated with RES1 ESK2 silicified cancer cells functionalized with Toll-like receptor (TLR) agonists (serving as a vaccine) are effective in controlling disease progression. When administered intraperitoneally, the vaccine predominantly localizes within the omental adipose tissue, specifically the omental milky spots (OMS), in mice with late-stage ovarian cancer. The observed therapeutic efficacy is attributed to the activation of regional T-cells residing within these specialized lymphoid structures. In contrast, subcutaneous or intravenous delivery results in vaccine accumulation in filtering organs, primarily the liver, and fails to elicit a therapeutic response. Notably, in a recent prophylactic study, subcutaneous vaccine administration reduced blocked tumor engraftment both systemically and within the peritoneal cavity, further underscoring the role of T-cells in mediating anti-tumor immunity. However, the immunosuppressive tumor microenvironment remains a significant barrier, leading to T-cell exhaustion and dysfunction. Therefore, a deeper understanding of the cellular interactions and mechanisms governing vaccine trafficking is essential for optimizing cancer immunotherapy. This study utilizes 3D Light Sheet microscopy to analyze the omentum, aiming to elucidate changes in the size and cellular composition of OMS as tumor progresses and in response to immune therapy. These insights may inform the development of more effective immunotherapeutic strategies for ovarian cancer. Citation Format: Ellie S. Kennedy, Rita E. Serda. Spatial dynamics of vaccine-induced immunity in ovarian cancer: The central role of omental milky spots abstract. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Ovarian Cancer Research; 2025 Sep 19-21; Denver, CO. Philadelphia (PA): AACR; Cancer Res 2025;85 (18Suppl): Abstract nr A034.