Neutrophil Extracellular Traps Promote Pre-Metastatic Niche Formation in the Omentum by Expanding Innate-Like B Cells That Express Il-10

Authors

WonJae Lee
Song Yi Ko
Hironari Akasaka
Melanie Weigert
Ernst Lengyel
Honami Naora

Language

English

Publication Date

1-13-2025

Journal

Cancer Cell

DOI

10.1016/j.ccell.2024.12.004

PMID

39753138

PMCID

PMC11732717

PubMedCentral® Posted Date

1-13-2026

PubMedCentral® Full Text Version

Author MSS

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 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.

Keywords

Extracellular Traps, Omentum, Animals, Female, Mice, Interleukin-10, Humans, Neutrophils, B-Lymphocytes, Ovarian Neoplasms, Peritoneal Neoplasms, Immunity, Innate, Mice, Inbred C57BL, Chemokine CXCL13, T-Lymphocytes, Regulatory, Protein Tyrosine Phosphatase, Non-Receptor Type 6, Mice, Knockout, Tumor Microenvironment, Neutrophil extracellular traps, Pre-metastatic niche, Omentum, Fat-associated lymphoid clusters

Published Open-Access

yes

Recommended Citation

Lee, WonJae; Ko, Song Yi; Akasaka, Hironari; et al., "Neutrophil Extracellular Traps Promote Pre-Metastatic Niche Formation in the Omentum by Expanding Innate-Like B Cells That Express Il-10" (2025). Faculty, Staff and Student Publications. 4878.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4878