High endothelial venules are present in pharyngeal and laryngeal carcinomas and they are associated with better prognosis

Karpathiou, Georgia; Dumollard, Jean Marc; Gavid, M.; Casteillo, François; Vieville, Marine; Prades, J.‐M.; Froudarakis, Marios; Péoc’h, Michel

doi:10.1016/j.prp.2021.153392

Cited by 13 publications

(7 citation statements)

References 18 publications

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“…The density of MECA-79 + TA-HEVs is positively correlated with clinical parameters indicative of reduced tumor progression and invasion in primary melanoma [ 29 , 246 , 247 ] and with increased metastasis-free survival and overall survival in primary breast cancer [ 28 ]. MECA-79 + TA-HEVs are also associated with increased lymphocyte infiltration, progression free-survival and overall survival in head and neck cancer [ 248 – 250 ]. Moreover, combined high densities of MECA-79 + TA-HEVs and CD8 + T cells are a prognostic factor for overall survival in gastric cancer [ 251 ].…”

Section: Tumor-associated Hevs (Ta-hevs) In Cancer Immunology and Immunotherapymentioning

confidence: 99%

“…Breslow tumor thickness is used as a prognostic biomarker for staging primary cutaneous melanomas and it was shown that densities of MECA-79 + TA-HEVs are inversely correlated with Breslow thickness, indicating that TA-HEVs are more abundant during the initial stages of melanoma [ 29 ]. Analysis of head and neck cancer with the tumor-node-metastasis (TNM) staging system revealed that T1 tumors exhibit higher densities of TA-HEVs as compared to tumors of later stages [ 248 , 249 ]. Interestingly, the progression from in situ to invasive ductal carcinoma is associated with a progressive loss of TA-HEVs in breast cancer [ 253 ].…”

Section: Tumor-associated Hevs (Ta-hevs) In Cancer Immunology and Immunotherapymentioning

confidence: 99%

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High endothelial venules (HEVs) in immunity, inflammation and cancer

2021

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High endothelial venules (HEVs) are specialized blood vessels mediating lymphocyte trafficking to lymph nodes (LNs) and other secondary lymphoid organs. By supporting high levels of lymphocyte extravasation from the blood, HEVs play an essential role in lymphocyte recirculation and immune surveillance for foreign invaders (bacterial and viral infections) and alterations in the body’s own cells (neoantigens in cancer). The HEV network expands during inflammation in immune-stimulated LNs and is profoundly remodeled in metastatic and tumor-draining LNs. HEV-like blood vessels expressing high levels of the HEV-specific sulfated MECA-79 antigens are induced in non-lymphoid tissues at sites of chronic inflammation in many human inflammatory and allergic diseases, including rheumatoid arthritis, Crohn’s disease, allergic rhinitis and asthma. Such vessels are believed to contribute to the amplification and maintenance of chronic inflammation. MECA-79+ tumor-associated HEVs (TA-HEVs) are frequently found in human tumors in CD3+ T cell-rich areas or CD20+ B-cell rich tertiary lymphoid structures (TLSs). TA-HEVs have been proposed to play important roles in lymphocyte entry into tumors, a process essential for successful antitumor immunity and lymphocyte-mediated cancer immunotherapy with immune checkpoint inhibitors, vaccines or adoptive T cell therapy. In this review, we highlight the phenotype and function of HEVs in homeostatic, inflamed and tumor-draining lymph nodes, and those of HEV-like blood vessels in chronic inflammatory diseases. Furthermore, we discuss the role and regulation of TA-HEVs in human cancer and mouse tumor models.

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Section: Tumor-associated Hevs (Ta-hevs) In Cancer Immunology and Immunotherapymentioning

confidence: 99%

Section: Tumor-associated Hevs (Ta-hevs) In Cancer Immunology and Immunotherapymentioning

confidence: 99%

High endothelial venules (HEVs) in immunity, inflammation and cancer

2021

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“…Moreover, tumour regression was positively correlated with HEV density in individuals with cutaneous melanoma 29,30 . However, to date, the function of HEV in ICC has never been reported.…”

Section: Discussionmentioning

confidence: 97%

“…Moreover, tumour regression was positively correlated with HEV density in individuals with cutaneous melanoma. 29 , 30 However, to date, the function of HEV in ICC has never been reported. Therefore, clarifying the impact of HEV on the immune microenvironment and the prognosis of individuals with ICC is essential.…”

Section: Discussionmentioning

confidence: 99%

High endothelial venule is a prognostic immune‐related biomarker in patients with resected intrahepatic cholangiocarcinoma

Zhou

Zhu

et al. 2023

Cell Proliferation

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Having been reported to be a crucial prognostic factor in solid tumours, the role of high endothelial venule (HEV) in intrahepatic cholangiocarcinoma (ICC) remains unclear, however. The data of ICC and healthy individuals were downloaded from the Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases. Meanwhile, a cutting‐edge ICC high‐resolution spatial transcriptome was also acquired before these data were comprehensively analysed using bioinformatics approaches. Moreover, 95 individuals with ICC who had undergone resection surgery were enrolled in this study to investigate the relationship between HEV and tumour microenvironment (TME) applying immunohistochemistry and multiple immunofluorescence techniques. The high‐HEV subtype contains rich immune infiltrates including tertiary lymphoid structure (TLS), CD8+ T cells, and CD20+ B cells. Furthermore, HEV and TLS exhibited a strong relationship of spatial colocalization. Correlated with improved prognostic outcomes in ICC, the high‐HEV subtype could be an independent prognostic indicator for individuals with ICC. This study revealed the association of HEV with immune function and observed a strong spatial colocalization correlation between HEV and TLS. Moreover, correlated with immunotherapeutic response, HEV could improve prognostic outcomes, which may be a potential indicator of immunotherapy pathology in ICC.

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“… 27 Additionally, patients with HEV had increased PFS and OS with pharyngeal, laryngeal, or oral cancer. 39 40 Furthermore, patients with cutaneous melanoma showed a positive correlation between tumor regression and HEV density. 41 However, a previous study to elucidate the role of HEV using tissue microarray in GC did not demonstrate the prognostic role of HEV.…”

Section: Discussionmentioning

confidence: 99%

High endothelial venule is a surrogate biomarker for T-cell inflamed tumor microenvironment and prognosis in gastric cancer

Park

Kim

et al. 2021

J Immunother Cancer

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BackgroundHigh endothelial venule (HEV) is a specialized vasculature for lymphocyte trafficking. While HEVs are frequently observed within gastric cancer (GC), the vascular–immune interaction between HEV and tumor-infiltrating lymphocytes (TILs) has not been well elucidated. In this study, we aimed to unveil the potential value of HEVs as a surrogate marker for T-cell inflamed immune microenvironment in GC using a large number of prospectively collected surgical specimens of GC.MethodsWe included 460 patients with GC who underwent surgical resection. Nanostring PanCancer immune profiling was performed to evaluate the immunological phenotype of GCs. HEV density and three distinct patterns of TILs (Crohn-like lymphoid reaction, peritumoral lymphoid reaction, and intratumoral lymphoid reaction) were analyzed for their relationship and evaluated as prognostic factors for relapse-free survival (RFS) and overall survival (OS).ResultsHEV-high GC revealed increased infiltration by immune cell subsets, including dendritic cells, CD8+ cytotoxic T cells, and CD4+ helper T cells. In addition, HEV-high GC demonstrated increased immune-modulating chemokines, type I or II interferon pathway, and immune checkpoints, all of which indicate the inflamed tumor microenvironment (TME). All three distinct patterns of TILs were associated with HEV density. In survival analysis, patients with HEV-high GC displayed significantly longer RFS and OS than those with HEV-low GC (p<0.001 for RFS, p<0.001 for OS). Multivariate analysis demonstrated that HEV was the most significant immunological prognostic factor for RFS (patients with high HEV compared with those with low HEV; HR 0.412, 95% CI 0.241 to 0.705, p=0.001) and OS (HR 0.547, 95% CI 0.329 to 0.909, p=0.02) after adjustment for age, stage, and TIL.ConclusionHEV is the most significant immunological prognosticator for RFS and OS in resected GC, indicating inflamed TME.

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High endothelial venules are present in pharyngeal and laryngeal carcinomas and they are associated with better prognosis

Cited by 13 publications

References 18 publications

High endothelial venules (HEVs) in immunity, inflammation and cancer

High endothelial venules (HEVs) in immunity, inflammation and cancer

High endothelial venule is a prognostic immune‐related biomarker in patients with resected intrahepatic cholangiocarcinoma

High endothelial venule is a surrogate biomarker for T-cell inflamed tumor microenvironment and prognosis in gastric cancer

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