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In an experimental mouse model of\n                    <jats:italic>Shb<\/jats:italic>\n                    \u2010gene deficiency in endothelial cells, breast cancer lung metastasis correlated with immune suppression rather than with vascular leakage. The present study aimed to assess underlying gene expression changes in endothelial and immune cells responsible for this phenotype and to explore their relationship to human disease. Mouse endothelial cell\n                    <jats:italic>Shb<\/jats:italic>\n                    \u2010gene deficiency, leading to \u2018vessel normalization\u2019, resulted in altered expression of chemo\/cytokine genes and upregulation of immune checkpoint genes in immune cells. Endothelial cells under these conditions exhibited gene expression patterns compatible with reduced angiogenesis and vascular leakage. Additionally, genes whose products relate to immune cell vascular transmigration and function were affected. In a human triple\u2010negative breast cancer cohort, tumors with reduced vascular leakage exhibited a higher relative proportion of regulatory T\u00a0cells and larger tumor size. However, these changes were not associated with increased metastasis. 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