文章标题：Palmitic acid reprograms neutrophils to compromise vascular integrity and promote breast cancer lung ｍmbedstasis

作者列表：Peng Qian, Yuxin Li, Yifeng Han, Chun Xu, Peng Zou, Fuming Yang, Xiaozhen Kang, Mengdi Wu, Jie Dong, Zhengyun Zou, Jiwu Wei

影响因子：26.3

期刊：IMMUNITY

发表时间：2026-4-24

DOI:10.1016/j.immuni.2026.03.026

文献主题：Highlights

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Pre-ｍmbedstatic lung accumulates palmitic acid during breast cancer progression

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Neutrophil-derived lipocalin-2 impairs pulmonary endothelial integrity

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Palmitic acid induces lipocalin-2 release through the TLR4-NF-κB signaling pathway

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Targeting endothelial fatty acid synthesis reduces breast cancer lung ｍmbedstasis

Summary

Pre-ｍmbedstatic niche ｆormation in the lung creates a permissive microenvironment for breast cancer ｍmbedstasis, characterized by ｍmbedbolic reprogramming of resident cells, recruitment of suppressive neutrophils, and vascular remodeling. However, the role of lipids in regulating neutrophil-endothelial interactions, particularly in facilitating tumor cell extravasation, remains largely undefined. Here, we showed that triple-negative breast cancer established a palmitic acid-enriched lung microenvironment that drove tumor cell extravasation and colonization. Pulmonary endothelial cells were a major source of palmitic acid, which activated neutrophils to produce lipocalin-2 (LCN2) via the Toll-like receptor 4 (TLR4)-NF-κB pathway. Neutrophil-derived LCN2 disrupted endothelial tight junctions, compromised vascular integrity, and facilitated tumor cell extravasation. Targeting endothelial fatty acid synthesis using glucagon-like peptide-1 receptor agonists preserved vascular integrity and suppressed lung ｍmbedstasis. These findings uncover a lipid-driven mechanism underlying ｍmbedstatic organotropism and highlight ｍmbedbolic intervention as a potential therapeutic strategy against breast cancer lung ｍmbedstasis.