Tumor-associated high endothelial venules are associated with enhanced lymphocyte infiltration and favorable prognosis in resected hepatocellular carcinoma
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Le résumé fourni par la source
BACKGROUND: Tumor-infiltrating lymphocytes (TILs) are essential to effective immunotherapy for hepatocellular carcinoma (HCC). Among factors regulating TILs, tumor-associated high endothelial venules (TA-HEVs) have been identified in various cancers and may contribute to TIL recruitment. This study aimed to investigate the clinical significance of TA-HEVs in HCC and their association with TILs. METHODS: 156 patients with HCC who underwent hepatic resection were analyzed. TA-HEVs were identified using double immunohistochemical staining for MECA-79 and CD31. Clinical outcomes and TIL density were compared between TA-HEV-present and -absent cases. Multicolor flow cytometry and RNA sequencing of tumor tissues were also performed. RESULTS: TA-HEVs were observed within tertiary lymphoid structures (TLSs) surrounding tumors in 31 of the 156 cases. The proportion of TLSs containing TA-HEVs increased with TLS maturation. TA-HEV-present cases had significantly better disease-free survival (3 years: 79.8% in TA-HEV-present cases vs 60.1% in TA-HEV-absent cases, p = 0.011). Multivariate analysis identified TA-HEVs as an independent favorable prognostic factor. Moreover, TA-HEV-present cases had significantly higher densities of intra-tumoral CD4⁺ and CD8⁺ T cells. RNA sequencing revealed enhanced pathways related to immune response and lymphocyte activation in TA-HEV-present cases, with high expression of cytotoxic lymphocyte markers. Flow cytometry confirmed elevated proportions of activated CD8⁺ T cells in TA-HEV-present cases. CONCLUSIONS: TA-HEVs in HCC were associated with significantly better prognosis and may contribute to immune activation within the tumor microenvironment.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Tumor-associated high endothelial venules are associated with enhanced lymphocyte infiltration and favorable prognosis in resected hepatocellular carcinoma
- Date Crossref
- 19/12/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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The University of Osaka pays non établi dans la noticeUniversité ou école supérieure
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Osaka Hospital pays non établi dans la noticeÉtablissement de santé
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Toyonaka Municipal Hospital Department of Gastroenterological Surgery pays non établi dans la noticeÉtablissement de santé
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Shionogi (Japan) pays non établi dans la noticeEntreprise
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Osaka Gakuin University pays non établi dans la noticeUniversité ou école supérieure
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Graduate School of Medicine Department of Clinical Research in Tumor Immunology pays non établi dans la noticeUniversité ou école supérieure
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Osaka Keisatsu Hospital Department of Gastroenterological Surgery pays non établi dans la noticeÉtablissement de santé
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Ltd. Shionogi & Co. pays non établi dans la noticeEntreprise
The University of Osaka, Osaka Hospital et Department of Gastroenterological Surgery — Toyonaka Municipal Hospital, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.