Abstract 6144: Peritoneal and omental macrophages provide anti-tumor immunity in an ovarian cancer model

Abstract The omentum is a visceral adipose tissue that contains fat-associated lymphoid clusters (FALC) to aid in peritoneal immunity. These clusters consist of large aggregates of B cells, T cells, dendritic cells, macrophages, and innate lymphoid cells that participate in the clearance of pathogens. Tissue-resident macrophages (TRM) are immune cells found in every tissue and their function is influenced by the local tissue microenvironment. TRM can be defined by their origins, consisting of subsets maintained either by embryonic precursors or by bone-marrow progenitors. A recent study found embryonically derived TRM express at least one marker amongst Tim4, LYVE1, FOLR2 while bone marrow derived macrophages maintain CCR2 expression. Previous publications have shown the existence of LYVE1+ macrophages surrounding each cluster, here we study an unexamined subset of FALC-associated macrophages that are imbedded within the lymphoid structures. Using confocal imaging, flow cytometry analysis with reporter/ conditional knock-out mice, we have characterized this TRM subset as CX3CR1+ LYVE1lo/- Tim4- and CCR2 dependent. Through Wt1-driven csf1 deletion, we depleted peritoneal and omental-resident (ORM) and found increased ID8 tumor cells in comparison to littermate controls. Lastly, promotion of CX3CR1+ ORM and reduction of LYVE1+ Tim4- ORM led to reduced tumor growth in the omentum in early-stage tumor challenge. Citation Format: Joseph R. Dominguez, Jiseon Kim, Seung Hyeon Kim, Yeonwoo Choi, Soroush Tahmasebi, Brahm H. Segal, Burkhard Ludewig, Ki-Wook Kim. Peritoneal and omental macrophages provide anti-tumor immunity in an ovarian cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6144.