{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T20:10:20Z","timestamp":1790021420092,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,17]]},"group-title":"Molecular Biology","reference-count":58,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"name":"Intramural Research Program of the National Institutes of Health, National Cancer Institute","award":["ZIA BC 012130"],"award-info":[{"award-number":["ZIA BC 012130"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Brain metastasis (BrM) is a devastating complication of triple-negative breast cancer (TNBC), yet how host macroenvironmental conditions influence brain metastatic susceptibility remains poorly understood. Here, we investigated the impact of deep vein thrombosis (DVT), a common complication in patients with cancer, on TNBC brain metastasis. Analysis of a large clinical cohort identified DVT as an independent risk factor for BrM in patients with metastatic breast cancer. Using two syngeneic TNBC models, we demonstrated that DVT selectively enhanced brain metastasis without significantly affecting primary tumor growth or lung metastasis. Mechanistically, DVT increased neutrophil accumulation in the brain metastatic microenvironment, and neutrophil depletion completely abrogated the metastasis-promoting effect of DVT. Single-cell RNA sequencing of CD45+ cells in peripheral blood revealed that DVT reprogrammed circulating neutrophils toward migratory and inflammatory transcriptomic profiles characterized by neutrophil extracellular trap (NET) formation. DVT increased CXCR2 expression on circulating neutrophils and enhanced neutrophil recruitment in brain. Moreover, DVT significantly increased circulating NETs. Collectively, our findings identify DVT as a systemic driver of TNBC brain metastasis and reveal that DVT primes circulating neutrophils toward enhanced vascular recruitment and NET formation, providing a mechanistic link between cancer-associated thrombosis and brain metastatic susceptibility.<\/jats:p>","DOI":"10.64898\/2026.09.15.751589","type":"posted-content","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:15:21Z","timestamp":1789676121000},"source":"Crossref","is-referenced-by-count":0,"title":["DVT-primed neutrophils reshape the brain microenvironment to promote brain metastasis"],"prefix":"10.64898","author":[{"given":"Shun","family":"Endo","sequence":"first","affiliation":[{"name":"Women\u2019s Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA"},{"name":"Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 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