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Herein, we used mouse models of hepatic metastatization to demonstrate that the continuous infusion of therapeutic doses of interferon-alpha (IFN\u03b1) controls CRC invasion by acting on hepatic endothelial cells (HECs). Mechanistically, IFN\u03b1 promoted the development of a vascular antimetastatic niche characterized by liver sinusoidal endothelial cells (LSECs) defenestration extracellular matrix and glycocalyx deposition, thus strengthening the liver vascular barrier impairing CRC trans-sinusoidal migration, without requiring a direct action on tumor cells, hepatic stellate cells, hepatocytes, or liver dendritic cells (DCs), Kupffer cells (KCs) and liver capsular macrophages (LCMs). Moreover, IFN\u03b1 endowed LSECs with efficient cross-priming potential that, along with the early intravascular tumor burden reduction, supported the generation of antitumor CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and ultimately led to the establishment of a protective long-term memory T cell response. These findings provide a rationale for the use of continuous IFN\u03b1 therapy in perioperative settings to reduce CRC metastatic spreading to the liver.\n                  <\/jats:p>","DOI":"10.7554\/elife.80690","type":"journal-article","created":{"date-parts":[[2022,9,19]],"date-time":"2022-09-19T09:15:12Z","timestamp":1663578912000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.80690","source":"Crossref","is-referenced-by-count":7,"title":["Continuous sensing of IFN\u03b1 by hepatic endothelial cells shapes a vascular antimetastatic barrier"],"prefix":"10.7554","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4270-376X","authenticated-orcid":true,"given":"Ngoc Lan","family":"Tran","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04tfzc498","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute","place":["Milan, 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