Presence of tumour high-endothelial venules is an independent positive prognostic factor and stratifies patients with advanced-stage oral squamous cell carcinoma

Wirsing, Anna Maria; Rikardsen, Oddveig G; Steigen, Sonja Eriksson; Uhlin‐Hansen, Lars; Hadler‐Olsen, Elin

doi:10.1007/s13277-015-4036-4

Cited by 20 publications

(42 citation statements)

References 38 publications

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“…Here, we show that sialyl 6‐sulfo LeX‐expressing HEV‐like vessels are induced in 65.9% of OSCC cases examined and report that these sialyl 6‐sulfo LeX‐positive HEV‐like vessels are induced more frequently in early compared to advanced OSCC. This finding is in line with a recent report by Wirsing and colleagues demonstrating that sialyl 6‐sulfo LeX‐positive HEV‐like vessels were present in all early OSCC cases examined but in two‐thirds of advanced cases . Martinet and colleagues previously reported that HEV‐like vessels are induced in lymphocyte‐rich areas of breast carcinoma and that vessel density is positively correlated with a favorable prognosis .…”

Section: Discussionsupporting

confidence: 91%

“…Recently, Wirsing et al reported that the presence of HEV‐like vessels in OSCC tissues is associated with lower disease‐specific death and that these HEV‐like vessels are more frequently induced in early (T1/T2) than in advanced (T3/T4) stages, suggesting that lymphocytes recruited via these vessels may function as cytotoxic effector cells to inhibit OSCC tumor growth . However, the extent to which such cytotoxic T cells are recruited through HEV‐like vessels remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Role of sialyl 6‐sulfo Lewis X in antitumor immunity against oral squamous cell carcinoma

Yoshida

Hoshino

Imamura

et al. 2017

J Oral Pathology Medicine

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Role of sialyl 6‐sulfo Lewis X in antitumor immunity against oral squamous cell carcinoma

Yoshida

Hoshino

Imamura

et al. 2017

J Oral Pathology Medicine

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“…High-endothelial venules are present in secondary lymphoid organs, and develop regularly in chronically inflamed tissue [15]. We have previously reported that the presence of high-endothelial venules is associated with improved survival in oral squamous cell carcinomas [16], which is in line with results from studies on melanoma and breast cancer [17,18]. However, these vessels are plastic, and their remodeling into regular blood vessels may impair lymphocyte recruitment and precede sentinel lymph node metastasis [19,20].…”

Section: Introductionmentioning

confidence: 55%

“…Sixty-eight percent of the patients received surgery in combination with radiotherapy, 15% concomitant radiotherapy and chemotherapy, 11% surgery in combination with local neck-dissection, 5% none or palliative therapy, and 1% were unknown. We retrieved clinical and histopathologic information from the patients' hospital files, pathology reports, and the Statistics of Norway, Cause of Death Registry, and have earlier published these data in studies analyzing the same patient cohort [16,30]. Pathological tumor staging was determined according to the most recent (second to fifth) TNM classification from the American Joint Committee on Cancer at the time of diagnosis.…”

Section: Patients and Materialsmentioning

confidence: 99%

“…In a cohort of 75 oral squamous cell carcinoma patients, we recently demonstrated that advanced-stage tumors with high-endothelial venules present were associated with a more pronounced inflammatory response and longer patient survival compared to their high-endothelial venule-negative counterpart [16]. In the present study on the same patient cohort, we explored the hypothesis that high-endothelial venules are master regulators of tumor immunity in oral squamous cell carcinoma by characterizing the immune cell infiltration and cytokine expression in relation to presence of such vessels.…”

Section: Introductionmentioning

confidence: 99%

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Presence of high-endothelial venules correlates with a favorable immune microenvironment in oral squamous cell carcinoma

et al. 2018

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Oral squamous cell carcinomas are associated with a poor prognosis, which may be partly due to functional impairment of the immune response. Lymphocyte recruitment to the tumor site is facilitated by high-endothelial venules, whereas expression of programmed-death ligand 1 (PD-L1) can impair T-cell function. Thus, we hypothesize that these factors are important in shaping the immune response in oral squamous cell carcinoma. In the present study, we characterized the immune infiltrate in formalin-fixed, paraffin-embedded tumor samples from 75 oral squamous cell carcinoma patients. We used immunohistochemistry to determine the distribution of immune cell subsets, high-endothelial venules, and PD-L1, as well as quantitative real-time polymerase chain reaction to assess the expression of inflammatory cytokines and chemokines associated with lymphocyte trafficking. Finally, we calculated correlations between the presence of immune cell subsets, the gene expression patterns, high-endothelial venules, PD-L1, and the clinicopathological parameters, including patient survival. The presence of high-endothelial venules correlated with increased number of CD3+ T cells and CD20+ B cells, higher levels of the chemokines CXCL12 and CCL21, and lower levels of CCL20, irrespective of the tumors' T stage. In univariate analysis, high levels of CD20+ B cells and CD68+ macrophages, positive high-endothelial venule status, and low T and N stages predicted longer patient survival. However, only the presence of high-endothelial venules and a low T stage were independent positive prognosticators. This indicates that high-endothelial venules are important mediators and a convenient marker of an antitumor immune response in oral squamous cell carcinoma. Our findings suggest that these vessels are a potential immunomodulatory target in this type of cancer. PD-L1 staining in tumor cells correlated with lower T stage, increased infiltration of CD4+ cells, and higher expression of several inflammation-related cytokines. Thus, oral squamous cell carcinomas rich in CD4+ cells may preferentially respond to PD-1/PD-L1 blockade therapy.

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Tertiary Lymphoid Organs: A Primer for Otolaryngologists

et al. 2020

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Objectives/Hypothesis: Lymphoid neogenesis or the development of organised, de novo lymphoid structures has been described increasingly in chronically inflamed tissues. The presence of tertiary lymphoid organs (TLOs) has already been demonstrated to result in significant consequences for disease pathology, severity, prognosis and patient outcomes. Whilst the wider medical community has embraced TLOs as important markers of disease and potential therapeutic targets, the otolaryngology field has only begun turning to these entities in an academic capacity. This review aims to outline the role of tertiary lymphoid organs in disease and summarise key early findings in the ENT field. We also an overview of TLOs, their developmental process and clinicopathological implications.Study design: Literature review. Methods: A literature search for all relevant peer-reviewed publications pertaining to TLOs and ENT diseases. Search was conducted using PubMed, Embase and CINAHL databases.Results: A total of 24 studies were identified relevant to the topic. The majority of TLO research in ENT fell into the areas of oral squamous cell carcinoma (SCC) and chronic rhinosinusitis (CRS).Conclusions: Early research into both oral SCC and CRS suggests that TLOs have significant roles within ear, nose and throat (ENT) diseases. At this point in time, however, TLOs remain somewhat a mystery amongst otolaryngologists. As information in this field increases, we may develop a better understanding of how lymphoid neogenesis can influence disease outcomes amongst our patients and, ultimately, how they can be utilised in an immunotherapeutic manner.

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Presence of tumour high-endothelial venules is an independent positive prognostic factor and stratifies patients with advanced-stage oral squamous cell carcinoma

Abstract: Background: Staging of oral squamous cell carcinoma is based on the TNM system, which has been deemed

Cited by 20 publications

References 38 publications

Role of sialyl 6‐sulfo Lewis X in antitumor immunity against oral squamous cell carcinoma

Role of sialyl 6‐sulfo Lewis X in antitumor immunity against oral squamous cell carcinoma

Presence of high-endothelial venules correlates with a favorable immune microenvironment in oral squamous cell carcinoma

Tertiary Lymphoid Organs: A Primer for Otolaryngologists

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