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dc.contributor.authorWirsing, Anna Maria
dc.contributor.authorErvik, Ida Korsnes
dc.contributor.authorSeppola, Marit
dc.contributor.authorUhlin-Hansen, Lars
dc.contributor.authorSteigen, Sonja Eriksson
dc.contributor.authorHadler-Olsen, Elin Synnøve
dc.date.accessioned2019-01-31T13:35:10Z
dc.date.available2019-01-31T13:35:10Z
dc.date.issued2018-02-07
dc.description.abstractOral 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.en_US
dc.description.sponsorshipThe North Norwegian Health Authoritiesen_US
dc.descriptionSource at <a href=https://doi.org/10.1038/s41379-018-0019-5>https://doi.org/10.1038/s41379-018-0019-5</a>. Please check the publisher's <a href=http://www.nature.com/authors/policies/license.html#terms>Terms of Reuse</a>.en_US
dc.identifier.citationWirsing, A.M., Ervik, I.K., Seppola, M., Uhlin-Hansen, L., Steigen, S.E. & Hadler-Olsen, E.S. (2018). Presence of high-endothelial venules correlates with a favorable immune microenvironment in oral squamous cell carcinoma. <i>Modern Pathology, 31</i>, 910-922. https://doi.org/10.1038/s41379-018-0019-5en_US
dc.identifier.cristinIDFRIDAID 1592830
dc.identifier.doi10.1038/s41379-018-0019-5
dc.identifier.issn0893-3952
dc.identifier.issn1530-0285
dc.identifier.urihttps://hdl.handle.net/10037/14575
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.relation.journalModern Pathology
dc.rights.accessRightsopenAccessen_US
dc.subjectVDP::Medical disciplines: 700::Clinical medical disciplines: 750::Oncology: 762en_US
dc.subjectVDP::Medisinske Fag: 700::Klinisk medisinske fag: 750::Onkologi: 762en_US
dc.titlePresence of high-endothelial venules correlates with a favorable immune microenvironment in oral squamous cell carcinomaen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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