{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T11:50:16Z","timestamp":1792410616397,"version":"4.4.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T00:00:00Z","timestamp":1792368000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Perivascular structures, in particular, perivascular spaces (PVS) are emerging key immune modulators in the tumor microenvironment. However, their relationship with immune infiltration, vascular remodeling, and clinical outcomes in brain metastases is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective two-center study, we analyzed 56 brain metastases. Perivascular spaces were graded on preoperatively T2-weighted MRI in the basal ganglia and centrum semiovale. Tumor immune infiltration, vascular features, and immune cell phenotypes were assessed by immunohistochemistry and spectral flow cytometry and correlated with clinical outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here we show that high PVS burden in the centrum semiovale region, but not in the basal ganglia, were significantly associated with improved overall survival. High PVS are linked to increased presence of tumor-infiltrating cytotoxic T cells\u2014most of which exhibited an activated\/exhausted phenotype, indicated by PD-1- and Fas-positivity\u2014was likewise prognostically favorable. Moreover, these cells showed elevated expression of the migration marker CXCR3, as well as Granzyme B\/IFN\u03b3 consistent with effector polarization. High PVS were additionally associated with a higher M1\/M2-like macrophage ratio, which showed similar prognostic relevance as high vascular density, suggesting enhanced blood supply and immune cell recruitment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings could establish PVS as a non-invasive imaging marker of anti-tumor immunity and prognosis in patients with brain metastasis, underscoring their potential as biomarkers for immune activity and therapeutic monitoring.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s43856-026-01918-7","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T11:04:51Z","timestamp":1792407891000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Perivascular spaces are associated with T cell trafficking and may have prognostic relevance in brain metastases"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8389-8439","authenticated-orcid":false,"given":"Claudia","family":"Maletzki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Michaelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sae-Yeon","family":"Won","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artem","family":"Refaelian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Freitag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Freiman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Onken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wasilewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Vajkoczy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawed","family":"Nawabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nico Noah","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Zimpfer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Cantr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Dubinski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,19]]},"reference":[{"key":"1918_CR1","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1016\/j.cell.2020.05.007","volume":"181","author":"F Klemm","year":"2020","unstructured":"Klemm, F. et al. 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F.G. received honoraria for lectures and travel expenses from AstraZeneca, BBraun Aesculap and Signus spine. F.G. received research funds from the Richard and Annemarie Wolf Foundation. F.G. received honoraria for travel expenses from the von Hippel Lindau association. F.G. participated in advisory board meetings for QV Bioelectronics. All other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"542"}}