Peritoneal and omental-resident macrophages provide anti-tumor immunity in an ovarian cancer model 3658

Abstract Description 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 mice lacking Csf1 in Wt1-expressing stromal cells and depletion of Csf1r in LYVE1-expressing cells, we found that the promotion of CX3CR1+ omental macrophages led to reduced tumor growth in early metastatic conditions. In conclusion, our study highlights CX3CR1+ omental macrophages as a key player in controlling ovarian tumor cell growth. Funding Sources T32HL007829; NIH R01-DK126753 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)