Presence of high-endothelial venules correlates with a favorable immune microenvironment in oral squamous cell carcinoma
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...
Gespeichert in:
| Veröffentlicht in: | Modern pathology 2018-06, Vol.31 (6), p.910-922 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 922 |
|---|---|
| container_issue | 6 |
| container_start_page | 910 |
| container_title | Modern pathology |
| container_volume | 31 |
| creator | Wirsing, Anna Maria Ervik, Ida Korsnes Seppola, Marit Uhlin-Hansen, Lars Steigen, Sonja Eriksson Hadler-Olsen, Elin |
| description | 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. |
| doi_str_mv | 10.1038/s41379-018-0019-5 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_crist</sourceid><recordid>TN_cdi_cristin_nora_10037_14575</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0893395222014922</els_id><sourcerecordid>1999679513</sourcerecordid><originalsourceid>FETCH-LOGICAL-c491t-b4f8ba5a8fffed73ef407b659c1d48ba0cd85e348f814a4fc0fab272c416a7f3</originalsourceid><addsrcrecordid>eNp9kUFvFSEUhYnR2Gf1B7hREjfdjMIAbyCuTGPVpIkuuicMc-mjmYEWZp76772TaTVx0RUkfOfcwz2EvObsPWdCf6iSi840jOuGMW4a9YTsuBKsYa1WT8mOaSMaYVR7Ql7UeoOMVLp9Tk5aI_mes25Hfv0oUCF5oDnQQ7w-NJCGPB9gjG6kR0jLCJX6XAqMbsbrzzgfqKPBHXNx_Qg0TtOSgE7RlwzpGEtOE6SZxkSRGGm9W9yUFzSBcaTeFR9TntxL8iy4scKr-_OUXF18vjr_2lx-__Lt_NNl46Xhc9PLoHunnA4hwNAJCJJ1_V4ZzweJL8wPWoGQOmgunQyeBde3Xevxg64L4pS83Wx9iXWOySYMZTljorO4jU4hcbYRtyXfLVBnO8W6ZnUJMLblxph9ZxQXiL77D73JS0kY37ZMSaaMFgwp_jAy11og2NsSJ1d-41i79ma33iz2Ztfe7Brizb3z0k8w_FU8FIVAuwEVn9I1lH-jH3P9uIkAF3yMKKo-rmUPsYCf7ZDjI-o_0lW3lA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2054059830</pqid></control><display><type>article</type><title>Presence of high-endothelial venules correlates with a favorable immune microenvironment in oral squamous cell carcinoma</title><source>MEDLINE</source><source>NORA - Norwegian Open Research Archives</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>ProQuest Central UK/Ireland</source><source>Alma/SFX Local Collection</source><creator>Wirsing, Anna Maria ; Ervik, Ida Korsnes ; Seppola, Marit ; Uhlin-Hansen, Lars ; Steigen, Sonja Eriksson ; Hadler-Olsen, Elin</creator><creatorcontrib>Wirsing, Anna Maria ; Ervik, Ida Korsnes ; Seppola, Marit ; Uhlin-Hansen, Lars ; Steigen, Sonja Eriksson ; Hadler-Olsen, Elin</creatorcontrib><description>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.</description><identifier>ISSN: 0893-3952</identifier><identifier>ISSN: 1530-0285</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/s41379-018-0019-5</identifier><identifier>PMID: 29416107</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>13/51 ; 38/1 ; 38/90 ; 631/67/327 ; 692/53/2422 ; Antitumor activity ; Biomarkers, Tumor ; Carcinoma, Squamous Cell - immunology ; Carcinoma, Squamous Cell - pathology ; CCL20 protein ; CCL21 protein ; CD20 antigen ; CD3 antigen ; CD4 antigen ; Chemokines ; Clinical medical disciplines: 750 ; CXCL12 protein ; Cytokines ; Endothelial Cells - immunology ; Endothelial Cells - pathology ; Gene expression ; Humans ; Immunohistochemistry ; Immunomodulation ; Inflammation ; Klinisk medisinske fag: 750 ; Laboratory Medicine ; Lymphocytes B ; Lymphocytes T ; Macrophages ; Medical disciplines: 700 ; Medical prognosis ; Medicine ; Medicine & Public Health ; Medisinske Fag: 700 ; Metastases ; Mouth Neoplasms - immunology ; Mouth Neoplasms - pathology ; Neoplasm Staging ; Oncology: 762 ; Onkologi: 762 ; Oral cancer ; Oral carcinoma ; Oral squamous cell carcinoma ; Paraffin ; Pathology ; PD-1 protein ; PD-L1 protein ; Polymerase chain reaction ; Prognosis ; Retrospective Studies ; Squamous cell carcinoma ; Tumor cells ; Tumor Microenvironment - immunology ; Tumors ; VDP ; Venules - immunology ; Venules - pathology</subject><ispartof>Modern pathology, 2018-06, Vol.31 (6), p.910-922</ispartof><rights>2018 United States & Canadian Academy of Pathology</rights><rights>United States & Canadian Academy of Pathology 2018</rights><rights>Copyright Nature Publishing Group Jun 2018</rights><rights>info:eu-repo/semantics/openAccess</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-b4f8ba5a8fffed73ef407b659c1d48ba0cd85e348f814a4fc0fab272c416a7f3</citedby><cites>FETCH-LOGICAL-c491t-b4f8ba5a8fffed73ef407b659c1d48ba0cd85e348f814a4fc0fab272c416a7f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2054059830?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>230,314,780,784,885,26567,27924,27925,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29416107$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wirsing, Anna Maria</creatorcontrib><creatorcontrib>Ervik, Ida Korsnes</creatorcontrib><creatorcontrib>Seppola, Marit</creatorcontrib><creatorcontrib>Uhlin-Hansen, Lars</creatorcontrib><creatorcontrib>Steigen, Sonja Eriksson</creatorcontrib><creatorcontrib>Hadler-Olsen, Elin</creatorcontrib><title>Presence of high-endothelial venules correlates with a favorable immune microenvironment in oral squamous cell carcinoma</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>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.</description><subject>13/51</subject><subject>38/1</subject><subject>38/90</subject><subject>631/67/327</subject><subject>692/53/2422</subject><subject>Antitumor activity</subject><subject>Biomarkers, Tumor</subject><subject>Carcinoma, Squamous Cell - immunology</subject><subject>Carcinoma, Squamous Cell - pathology</subject><subject>CCL20 protein</subject><subject>CCL21 protein</subject><subject>CD20 antigen</subject><subject>CD3 antigen</subject><subject>CD4 antigen</subject><subject>Chemokines</subject><subject>Clinical medical disciplines: 750</subject><subject>CXCL12 protein</subject><subject>Cytokines</subject><subject>Endothelial Cells - immunology</subject><subject>Endothelial Cells - pathology</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Immunomodulation</subject><subject>Inflammation</subject><subject>Klinisk medisinske fag: 750</subject><subject>Laboratory Medicine</subject><subject>Lymphocytes B</subject><subject>Lymphocytes T</subject><subject>Macrophages</subject><subject>Medical disciplines: 700</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Medisinske Fag: 700</subject><subject>Metastases</subject><subject>Mouth Neoplasms - immunology</subject><subject>Mouth Neoplasms - pathology</subject><subject>Neoplasm Staging</subject><subject>Oncology: 762</subject><subject>Onkologi: 762</subject><subject>Oral cancer</subject><subject>Oral carcinoma</subject><subject>Oral squamous cell carcinoma</subject><subject>Paraffin</subject><subject>Pathology</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Polymerase chain reaction</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><subject>Squamous cell carcinoma</subject><subject>Tumor cells</subject><subject>Tumor Microenvironment - immunology</subject><subject>Tumors</subject><subject>VDP</subject><subject>Venules - immunology</subject><subject>Venules - pathology</subject><issn>0893-3952</issn><issn>1530-0285</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>3HK</sourceid><recordid>eNp9kUFvFSEUhYnR2Gf1B7hREjfdjMIAbyCuTGPVpIkuuicMc-mjmYEWZp76772TaTVx0RUkfOfcwz2EvObsPWdCf6iSi840jOuGMW4a9YTsuBKsYa1WT8mOaSMaYVR7Ql7UeoOMVLp9Tk5aI_mes25Hfv0oUCF5oDnQQ7w-NJCGPB9gjG6kR0jLCJX6XAqMbsbrzzgfqKPBHXNx_Qg0TtOSgE7RlwzpGEtOE6SZxkSRGGm9W9yUFzSBcaTeFR9TntxL8iy4scKr-_OUXF18vjr_2lx-__Lt_NNl46Xhc9PLoHunnA4hwNAJCJJ1_V4ZzweJL8wPWoGQOmgunQyeBde3Xevxg64L4pS83Wx9iXWOySYMZTljorO4jU4hcbYRtyXfLVBnO8W6ZnUJMLblxph9ZxQXiL77D73JS0kY37ZMSaaMFgwp_jAy11og2NsSJ1d-41i79ma33iz2Ztfe7Brizb3z0k8w_FU8FIVAuwEVn9I1lH-jH3P9uIkAF3yMKKo-rmUPsYCf7ZDjI-o_0lW3lA</recordid><startdate>20180601</startdate><enddate>20180601</enddate><creator>Wirsing, Anna Maria</creator><creator>Ervik, Ida Korsnes</creator><creator>Seppola, Marit</creator><creator>Uhlin-Hansen, Lars</creator><creator>Steigen, Sonja Eriksson</creator><creator>Hadler-Olsen, Elin</creator><general>Elsevier Inc</general><general>Nature Publishing Group US</general><general>Elsevier Limited</general><general>Springer Nature</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>3HK</scope></search><sort><creationdate>20180601</creationdate><title>Presence of high-endothelial venules correlates with a favorable immune microenvironment in oral squamous cell carcinoma</title><author>Wirsing, Anna Maria ; Ervik, Ida Korsnes ; Seppola, Marit ; Uhlin-Hansen, Lars ; Steigen, Sonja Eriksson ; Hadler-Olsen, Elin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-b4f8ba5a8fffed73ef407b659c1d48ba0cd85e348f814a4fc0fab272c416a7f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>13/51</topic><topic>38/1</topic><topic>38/90</topic><topic>631/67/327</topic><topic>692/53/2422</topic><topic>Antitumor activity</topic><topic>Biomarkers, Tumor</topic><topic>Carcinoma, Squamous Cell - immunology</topic><topic>Carcinoma, Squamous Cell - pathology</topic><topic>CCL20 protein</topic><topic>CCL21 protein</topic><topic>CD20 antigen</topic><topic>CD3 antigen</topic><topic>CD4 antigen</topic><topic>Chemokines</topic><topic>Clinical medical disciplines: 750</topic><topic>CXCL12 protein</topic><topic>Cytokines</topic><topic>Endothelial Cells - immunology</topic><topic>Endothelial Cells - pathology</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Immunomodulation</topic><topic>Inflammation</topic><topic>Klinisk medisinske fag: 750</topic><topic>Laboratory Medicine</topic><topic>Lymphocytes B</topic><topic>Lymphocytes T</topic><topic>Macrophages</topic><topic>Medical disciplines: 700</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Medisinske Fag: 700</topic><topic>Metastases</topic><topic>Mouth Neoplasms - immunology</topic><topic>Mouth Neoplasms - pathology</topic><topic>Neoplasm Staging</topic><topic>Oncology: 762</topic><topic>Onkologi: 762</topic><topic>Oral cancer</topic><topic>Oral carcinoma</topic><topic>Oral squamous cell carcinoma</topic><topic>Paraffin</topic><topic>Pathology</topic><topic>PD-1 protein</topic><topic>PD-L1 protein</topic><topic>Polymerase chain reaction</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><topic>Squamous cell carcinoma</topic><topic>Tumor cells</topic><topic>Tumor Microenvironment - immunology</topic><topic>Tumors</topic><topic>VDP</topic><topic>Venules - immunology</topic><topic>Venules - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wirsing, Anna Maria</creatorcontrib><creatorcontrib>Ervik, Ida Korsnes</creatorcontrib><creatorcontrib>Seppola, Marit</creatorcontrib><creatorcontrib>Uhlin-Hansen, Lars</creatorcontrib><creatorcontrib>Steigen, Sonja Eriksson</creatorcontrib><creatorcontrib>Hadler-Olsen, Elin</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>NORA - Norwegian Open Research Archives</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wirsing, Anna Maria</au><au>Ervik, Ida Korsnes</au><au>Seppola, Marit</au><au>Uhlin-Hansen, Lars</au><au>Steigen, Sonja Eriksson</au><au>Hadler-Olsen, Elin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Presence of high-endothelial venules correlates with a favorable immune microenvironment in oral squamous cell carcinoma</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2018-06-01</date><risdate>2018</risdate><volume>31</volume><issue>6</issue><spage>910</spage><epage>922</epage><pages>910-922</pages><issn>0893-3952</issn><issn>1530-0285</issn><eissn>1530-0285</eissn><abstract>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.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>29416107</pmid><doi>10.1038/s41379-018-0019-5</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0893-3952 |
| ispartof | Modern pathology, 2018-06, Vol.31 (6), p.910-922 |
| issn | 0893-3952 1530-0285 1530-0285 |
| language | eng |
| recordid | cdi_cristin_nora_10037_14575 |
| source | MEDLINE; NORA - Norwegian Open Research Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ProQuest Central UK/Ireland; Alma/SFX Local Collection |
| subjects | 13/51 38/1 38/90 631/67/327 692/53/2422 Antitumor activity Biomarkers, Tumor Carcinoma, Squamous Cell - immunology Carcinoma, Squamous Cell - pathology CCL20 protein CCL21 protein CD20 antigen CD3 antigen CD4 antigen Chemokines Clinical medical disciplines: 750 CXCL12 protein Cytokines Endothelial Cells - immunology Endothelial Cells - pathology Gene expression Humans Immunohistochemistry Immunomodulation Inflammation Klinisk medisinske fag: 750 Laboratory Medicine Lymphocytes B Lymphocytes T Macrophages Medical disciplines: 700 Medical prognosis Medicine Medicine & Public Health Medisinske Fag: 700 Metastases Mouth Neoplasms - immunology Mouth Neoplasms - pathology Neoplasm Staging Oncology: 762 Onkologi: 762 Oral cancer Oral carcinoma Oral squamous cell carcinoma Paraffin Pathology PD-1 protein PD-L1 protein Polymerase chain reaction Prognosis Retrospective Studies Squamous cell carcinoma Tumor cells Tumor Microenvironment - immunology Tumors VDP Venules - immunology Venules - pathology |
| title | Presence of high-endothelial venules correlates with a favorable immune microenvironment in oral squamous cell carcinoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T01%3A35%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_crist&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Presence%20of%20high-endothelial%20venules%20correlates%20with%20a%20favorable%20immune%20microenvironment%20in%20oral%20squamous%20cell%20carcinoma&rft.jtitle=Modern%20pathology&rft.au=Wirsing,%20Anna%20Maria&rft.date=2018-06-01&rft.volume=31&rft.issue=6&rft.spage=910&rft.epage=922&rft.pages=910-922&rft.issn=0893-3952&rft.eissn=1530-0285&rft_id=info:doi/10.1038/s41379-018-0019-5&rft_dat=%3Cproquest_crist%3E1999679513%3C/proquest_crist%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2054059830&rft_id=info:pmid/29416107&rft_els_id=S0893395222014922&rfr_iscdi=true |