美国德克萨斯大学Honami Naora团队发现，中性粒细胞外陷阱通过扩增表达IL-10的类固有B细胞在大网膜中促进转移前微环境的形成。相关论文于2025年1月2日在线发表在《癌细胞》杂志上。

据了解，腹腔液中的播散性癌细胞常常定植于大网膜脂肪相关淋巴小体，但其机制尚不清楚。

研究人员发现类固有B细胞在早期卵巢癌小鼠和女性的大网膜中积累，并伴随着中性粒细胞通过外排染色质纤维形成的中性粒细胞外陷阱（NET）。使用基因修饰的NET缺失小鼠、药物抑制NET以及过继性B细胞转移的研究表明，NET在转移前大网膜中诱导趋化因子CXCL13的表达，刺激腹腔类固有B细胞的招募。

这些B细胞通过产生白介素（IL）-10进一步促进调节性T细胞的扩增和大网膜转移。体外研究表明，NET通过失活B细胞激活通路抑制酶SHP-1以及生成活性氧（ROS）来诱导类固有B细胞产生IL-10。这些发现揭示NET改变了转移前大网膜中的免疫细胞动态，使该微环境有利于癌细胞定植。

附：英文原文

Title: Neutrophil extracellular traps promote pre-metastatic niche formation in the omentum by expanding innate-like B cells that express IL-10

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

Issue&Volume: 2025-01-02

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.

DOI: 10.1016/j.ccell.2024.12.004

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(24)00479-3