{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T12:44:59Z","timestamp":1782909899441,"version":"3.54.5"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T00:00:00Z","timestamp":1778198400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":54,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Korea government","award":["RS-2023-00275161"],"award-info":[{"award-number":["RS-2023-00275161"]}]},{"name":"Korea government","award":["M-2022-C0460-00037"],"award-info":[{"award-number":["M-2022-C0460-00037"]}]},{"name":"Korea government","award":["RS-2020-NR048734"],"award-info":[{"award-number":["RS-2020-NR048734"]}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"crossref","award":["HR21C1003"],"award-info":[{"award-number":["HR21C1003"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Asan Institute for Life Sciences","award":["2024IL0001"],"award-info":[{"award-number":["2024IL0001"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tumor-associated high endothelial venules (TA-HEVs) mediate lymphocyte trafficking into tumors and modulate the tumor microenvironment, with reported effects on clinical outcomes. However, reports have described discordant associations across cancers and microenvironmental contexts. Studies on state-specific, pan-cancer analyses of TA-HEV function remain limited. We integrated publicly available single-cell RNA sequencing datasets from 11 cancer types. Functional features of TA-HEVs were inferred by pathway enrichment and single-cell gene-set scoring for pathway gene sets. State-specific programs were applied to The Cancer Genome Atlas dataset to assess their clinical impact. We constructed a comprehensive atlas of tumor-associated endothelial cells and identified TA-HEV subclusters. Five TA-HEV subclusters were grouped into two functional states: inflammatory and stress-metabolic. The inflammatory TA-HEVs were enriched for innate immune stimulation, cytokine\/chemokine signaling, and MHC class II antigen presentation, whereas the stress-metabolic TA-HEVs were characterized by the unfolded protein response, heat shock pathways, oxidative phosphorylation, and ATP biosynthesis. Across cancers, the stress-metabolic TA-HEV state was generally associated with worse prognosis, while the inflammatory TA-HEV state showed context-dependent associations. Together, these findings define TA-HEVs as a heterogeneous endothelial population comprising distinct functional states with divergent clinical associations, providing a pan-cancer framework for interpreting TA-HEV signals in tumor biology.<\/jats:p>","DOI":"10.1007\/s12672-026-05162-2","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T09:05:01Z","timestamp":1778490301000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptional heterogeneity of tumor-associated high endothelial venules defines inflammatory and stress-metabolic states with distinct prognostic associations"],"prefix":"10.1007","volume":"17","author":[{"given":"Hwal-Seok","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Woo","family":"Choi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Jeong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunji","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Kyung","family":"Pak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Roh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chan-Sik","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,8]]},"reference":[{"key":"5162_CR1","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1038\/nm.3394","volume":"19","author":"DF Quail","year":"2013","unstructured":"Quail DF, Joyce JA. 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