Abstract 1360: Neutrophil extracellular traps establish the pre-metastatic niche in the omentum by expanding innate-like B cells that express IL-10

Abstract Disseminated cancer cells in the peritoneal fluid frequently implant on the omentum, an immune cell-rich fatty tissue that drapes from the stomach, but the underlying mechanisms are poorly understood. In this study, we identified that innate-like B cells accumulate in the uninvolved omentum of mice and women with early-stage ovarian cancer concomitantly with the release of chromatin fibers by neutrophils called neutrophil extracellular traps (NETs). Studies using genetically modified NET-deficient mice, pharmacologic inhibition of NETs, and adoptive B cell transfer showed that NETs induce expression of the chemokine CXCL13 in mesothelial cells in the pre-metastatic omentum, stimulating recruitment of innate-like B cells from the peritoneal cavity. Furthermore, studies using IL-10-reporter mice showed that NETs stimulate innate-like B cells to produce IL-10 that in turn expands regulatory T cells in the pre-metastatic omentum and potentiates metastasis at this site. Ex vivo studies showed that NETs elicit IL-10 production in innate-like B cells by generating reactive oxygen species and by inactivating SHP-1, a phosphatase that inhibits B cell activation pathways, through dissociating SHP-1 from CD22. These findings reveal that NETs alter immune cell dynamics in the pre-metastatic omentum and render this niche permissive for cancer cell colonization. Citation Format: WonJae Lee, Song Yi Ko, Hironari Akasaka, Melanie Weigert, Ernst Lengyel, Honami Naora. Neutrophil extracellular traps establish the pre-metastatic niche in the omentum by expanding innate-like B cells that express IL-10 [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 1360.