LYVE1+ macrophages of murine peritoneal mesothelium promote omentum-independent ovarian tumor growth

Abstract

Two resident macrophage subsets reside in peritoneal fluid. Macrophages also reside within mesothelial membranes lining the peritoneal cavity, but they remain poorly characterized. Here, we identified two macrophage populations (LYVE1^hi MHC II^lo-hi CX₃CR1gfp^lo/− and LYVE1^lo/− MHC II^hi CX₃CR1gfp^hi subsets) in the mesenteric and parietal mesothelial linings of the peritoneum. These macrophages resembled LYVE1⁺ macrophages within surface membranes of numerous organs. Fate-mapping approaches and analysis of newborn mice showed that LYVE1^hi macrophages predominantly originated from embryonic-derived progenitors and were controlled by CSF1 made by Wt1⁺ stromal cells. Their gene expression profile closely overlapped with ovarian tumor-associated macrophages previously described in the omentum. Indeed, syngeneic epithelial ovarian tumor growth was strongly reduced following in vivo ablation of LYVE1^hi macrophages, including in mice that received omentectomy to dissociate the role from omental macrophages. These data reveal that the peritoneal compartment contains at least four resident macrophage populations and that LYVE1^hi mesothelial macrophages drive tumor growth independently of the omentum.