ArticleCancer immunology, immunotherapy : CII2025
Tumor-associated high endothelial venules are associated with enhanced lymphocyte infiltration and favorable prognosis in resected hepatocellular carcinoma.
Article in Cancer immunology, immunotherapy : CII, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed.
- Review
- Tertiary lymphoid structures in cancer: their development, composition, clinical prognosis, and the drivers of the anti-tumor responses.Molecular biomedicine · 2026Review
- NOS2 and COX2 impact the spatial landscape of CD8Redox biology · 2026Review
- The impact of local tumor immune responses on prognosis in resected lung adenocarcinoma.Translational lung cancer research · 2026Article
- Clinical and prognostic significance of high-endothelial venule density in regional lymph nodes of esophageal adenocarcinoma.Frontiers in oncology · 2026Article
- Tertiary lymphoid structures in neoadjuvant and perioperative cancer immunotherapy: a review and proposed framework for biomarker interpretation and validation.Frontiers in immunology · 2026Review
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Abstract
backgroundTumor-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.
methods156 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.
resultsTA-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.
conclusionsTA-HEVs in HCC were associated with significantly better prognosis and may contribute to immune activation within the tumor microenvironment.
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