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University of Texas MD Anderson Cancer Center

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Cancer Cell, Available online 2 January 2025 | https://doi.org/10.1016/j.ccell.2024.12.004 Neutrophil extracellular traps promote pre-metastatic niche formation in the omentum by expanding innate-like B cells that express IL-10

WonJae Lee ¹, Song Yi Ko ¹, Hironari Akasaka ¹, Melanie Weigert ², Ernst Lengyel ², Honami Naora ^1,3

¹Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
²Department of Obstetrics and Gynecology, The University of Chicago, Chicago, IL 60637, USA
³Lead contact

Corresponding author : Honami Naora

Abstract

Disseminated cancer cells in the peritoneal fluid often colonize omental fat-associated lymphoid clusters but the mechanisms are unclear. Here, we identify that innate-like B cells accumulate in the omentum of mice and women with early-stage ovarian cancer concomitantly with the extrusion 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 show that NETs induce expression of the chemoattractant CXCL13 in the pre-metastatic omentum, stimulating recruitment of peritoneal innate-like B cells that in turn promote expansion of regulatory T cells and omental metastasis through producing interleukin (IL)-10. Ex vivo studies show that NETs elicit IL-10 production in innate-like B cells by inactivating SHP-1, a phosphatase that inhibits B cell activation pathways, and by generating reactive oxygen species. These findings reveal that NETs alter immune cell dynamics in the pre-metastatic omentum, rendering this niche conducive for colonization.

논문정보

형식Research article
게재일2025년 01월 (BRIC 등록일 2025-01-08)
연구진국외 연구진
분야 생명과학 > 노화/암생물학

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