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PD‐L1 expression patterns in oral cancer as an integrated approach for further prognostic classification
Background Despite the well‐known role of programmed cell death ligand 1 (PD‐L1) in promoting immune resistance in oral squamous cell carcinoma (OSCC), its potential utility as a prognostic biomarker is undetermined. We evaluated PD‐L1 expression as predictor of survival in patients with OSCC and ex...
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Published in: | Oral diseases 2021-10, Vol.27 (7), p.1699-1710 |
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container_title | Oral diseases |
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creator | Miranda‐Galvis, Marisol Rumayor Piña, Alicia Sales de Sá, Raísa Almeida Leite, Amanda Agustin Vargas, Pablo Calsavara, Vinicius Fernando Lópes Pinto, Clóvis A. Teng, Yong Kowalski, Luiz Paulo |
description | Background
Despite the well‐known role of programmed cell death ligand 1 (PD‐L1) in promoting immune resistance in oral squamous cell carcinoma (OSCC), its potential utility as a prognostic biomarker is undetermined. We evaluated PD‐L1 expression as predictor of survival in patients with OSCC and explored PD‐L1 expression patterns.
Methods
We conducted a retrospective cohort study that assessed PD‐L1 expression through immunohistochemistry in 123 surgical specimens of OSCC. A first approach evaluated tumor proportion scores (TPS) and combined proportion scores (CPS). Next, expression patterns were examined by evaluating PD‐L1 localization in tumor nests, as well as the interfaces of tumor cells (TC) and immune cells (IC) in the tumor microenvironment.
Results
High‐level PD‐L1 expression determined by TPS and CPS using variable cutoffs was not associated with survival. Immunohistochemistry revealed that TC expressed PD‐L1 in either patchy or diffuse patterns. The patchy pattern was an independent risk factor for overall survival. Furthermore, expression patterns in the tumor immune microenvironment showed that most cases expressed PD‐L1 on both TC and IC, while PD‐L1 non‐expressors had the lowest overall survival.
Conclusion
PD‐L1 expression patterns in the context of localization in tumor nests and TC—IC interactions represent antitumor immune responses better than either TPS or CPS. Our suggested classification system may have important implications for the characterization of OSCC and for the use of PD‐L1 as a prognostic biomarker. |
doi_str_mv | 10.1111/odi.13714 |
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Despite the well‐known role of programmed cell death ligand 1 (PD‐L1) in promoting immune resistance in oral squamous cell carcinoma (OSCC), its potential utility as a prognostic biomarker is undetermined. We evaluated PD‐L1 expression as predictor of survival in patients with OSCC and explored PD‐L1 expression patterns.
Methods
We conducted a retrospective cohort study that assessed PD‐L1 expression through immunohistochemistry in 123 surgical specimens of OSCC. A first approach evaluated tumor proportion scores (TPS) and combined proportion scores (CPS). Next, expression patterns were examined by evaluating PD‐L1 localization in tumor nests, as well as the interfaces of tumor cells (TC) and immune cells (IC) in the tumor microenvironment.
Results
High‐level PD‐L1 expression determined by TPS and CPS using variable cutoffs was not associated with survival. Immunohistochemistry revealed that TC expressed PD‐L1 in either patchy or diffuse patterns. The patchy pattern was an independent risk factor for overall survival. Furthermore, expression patterns in the tumor immune microenvironment showed that most cases expressed PD‐L1 on both TC and IC, while PD‐L1 non‐expressors had the lowest overall survival.
Conclusion
PD‐L1 expression patterns in the context of localization in tumor nests and TC—IC interactions represent antitumor immune responses better than either TPS or CPS. Our suggested classification system may have important implications for the characterization of OSCC and for the use of PD‐L1 as a prognostic biomarker.</description><identifier>ISSN: 1354-523X</identifier><identifier>EISSN: 1601-0825</identifier><identifier>DOI: 10.1111/odi.13714</identifier><identifier>PMID: 33169454</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Antitumor activity ; Apoptosis ; B7-H1 Antigen ; Biomarkers ; Carcinoma, Squamous Cell ; Cell death ; expression pattern ; Head and Neck Neoplasms ; Humans ; immune microenvironment ; Immune response ; Immunohistochemistry ; Interfaces ; Localization ; Mouth Neoplasms ; Oral cancer ; Oral carcinoma ; Oral squamous cell carcinoma ; PD-L1 protein ; Prognosis ; programmed cell death ligand 1 ; Retrospective Studies ; Risk factors ; score ; Squamous cell carcinoma ; Tumor cells ; Tumor Microenvironment</subject><ispartof>Oral diseases, 2021-10, Vol.27 (7), p.1699-1710</ispartof><rights>2020 Wiley Periodicals LLC</rights><rights>2020 Wiley Periodicals LLC.</rights><rights>2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3534-be1d5389dbf48219e42b9a50776952c93409fe3dafe251467b39e20a67ffedd43</citedby><cites>FETCH-LOGICAL-c3534-be1d5389dbf48219e42b9a50776952c93409fe3dafe251467b39e20a67ffedd43</cites><orcidid>0000-0003-4798-584X ; 0000-0002-0481-156X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33169454$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miranda‐Galvis, Marisol</creatorcontrib><creatorcontrib>Rumayor Piña, Alicia</creatorcontrib><creatorcontrib>Sales de Sá, Raísa</creatorcontrib><creatorcontrib>Almeida Leite, Amanda</creatorcontrib><creatorcontrib>Agustin Vargas, Pablo</creatorcontrib><creatorcontrib>Calsavara, Vinicius Fernando</creatorcontrib><creatorcontrib>Lópes Pinto, Clóvis A.</creatorcontrib><creatorcontrib>Teng, Yong</creatorcontrib><creatorcontrib>Kowalski, Luiz Paulo</creatorcontrib><title>PD‐L1 expression patterns in oral cancer as an integrated approach for further prognostic classification</title><title>Oral diseases</title><addtitle>Oral Dis</addtitle><description>Background
Despite the well‐known role of programmed cell death ligand 1 (PD‐L1) in promoting immune resistance in oral squamous cell carcinoma (OSCC), its potential utility as a prognostic biomarker is undetermined. We evaluated PD‐L1 expression as predictor of survival in patients with OSCC and explored PD‐L1 expression patterns.
Methods
We conducted a retrospective cohort study that assessed PD‐L1 expression through immunohistochemistry in 123 surgical specimens of OSCC. A first approach evaluated tumor proportion scores (TPS) and combined proportion scores (CPS). Next, expression patterns were examined by evaluating PD‐L1 localization in tumor nests, as well as the interfaces of tumor cells (TC) and immune cells (IC) in the tumor microenvironment.
Results
High‐level PD‐L1 expression determined by TPS and CPS using variable cutoffs was not associated with survival. Immunohistochemistry revealed that TC expressed PD‐L1 in either patchy or diffuse patterns. The patchy pattern was an independent risk factor for overall survival. Furthermore, expression patterns in the tumor immune microenvironment showed that most cases expressed PD‐L1 on both TC and IC, while PD‐L1 non‐expressors had the lowest overall survival.
Conclusion
PD‐L1 expression patterns in the context of localization in tumor nests and TC—IC interactions represent antitumor immune responses better than either TPS or CPS. Our suggested classification system may have important implications for the characterization of OSCC and for the use of PD‐L1 as a prognostic biomarker.</description><subject>Antitumor activity</subject><subject>Apoptosis</subject><subject>B7-H1 Antigen</subject><subject>Biomarkers</subject><subject>Carcinoma, Squamous Cell</subject><subject>Cell death</subject><subject>expression pattern</subject><subject>Head and Neck Neoplasms</subject><subject>Humans</subject><subject>immune microenvironment</subject><subject>Immune response</subject><subject>Immunohistochemistry</subject><subject>Interfaces</subject><subject>Localization</subject><subject>Mouth Neoplasms</subject><subject>Oral cancer</subject><subject>Oral carcinoma</subject><subject>Oral squamous cell carcinoma</subject><subject>PD-L1 protein</subject><subject>Prognosis</subject><subject>programmed cell death ligand 1</subject><subject>Retrospective Studies</subject><subject>Risk factors</subject><subject>score</subject><subject>Squamous cell carcinoma</subject><subject>Tumor cells</subject><subject>Tumor Microenvironment</subject><issn>1354-523X</issn><issn>1601-0825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNp1kc1uEzEQxy1ERdLAgRdAlrjAYVN_ruMjaviIFCkcQOJmeb3jZKPNerF3BbnxCH1GnqSm2_aA1LnMaPTTT6P5I_SakiXNdRXqZkm5ouIZmtOS0IKsmHyeZy5FIRn_MUOXKR0JoUpz9gLNOKelFlLM0fHr-u-fmy3F8LuPkFITOtzbYYDYJdx0OETbYmc7BxHbhG2XlwPsox2gxrbvY7DugH2I2I9xOGQqr_ZdSEPjsGttNvrG2SF7X6ILb9sEr-77An3_9PHb9Zdiu_u8uf6wLRyXXBQV0Fryla4rL1aMahCs0lYSpUotmdNcEO2B19YDk1SUquIaGLGl8h7qWvAFejd58yU_R0iDOTXJQdvaDsKYDBNS8_wVzjL69j_0GMbY5esMk0pxXRK1ytT7iXIxpBTBmz42JxvPhhLzLwCTAzB3AWT2zb1xrE5QP5IPH8_A1QT8alo4P20yu_VmUt4CCLyQmQ</recordid><startdate>202110</startdate><enddate>202110</enddate><creator>Miranda‐Galvis, Marisol</creator><creator>Rumayor Piña, Alicia</creator><creator>Sales de Sá, Raísa</creator><creator>Almeida Leite, Amanda</creator><creator>Agustin Vargas, Pablo</creator><creator>Calsavara, Vinicius Fernando</creator><creator>Lópes Pinto, Clóvis A.</creator><creator>Teng, Yong</creator><creator>Kowalski, Luiz Paulo</creator><general>Wiley Subscription Services, Inc</general><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>7QP</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4798-584X</orcidid><orcidid>https://orcid.org/0000-0002-0481-156X</orcidid></search><sort><creationdate>202110</creationdate><title>PD‐L1 expression patterns in oral cancer as an integrated approach for further prognostic classification</title><author>Miranda‐Galvis, Marisol ; Rumayor Piña, Alicia ; Sales de Sá, Raísa ; Almeida Leite, Amanda ; Agustin Vargas, Pablo ; Calsavara, Vinicius Fernando ; Lópes Pinto, Clóvis A. ; Teng, Yong ; Kowalski, Luiz Paulo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3534-be1d5389dbf48219e42b9a50776952c93409fe3dafe251467b39e20a67ffedd43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antitumor activity</topic><topic>Apoptosis</topic><topic>B7-H1 Antigen</topic><topic>Biomarkers</topic><topic>Carcinoma, Squamous Cell</topic><topic>Cell death</topic><topic>expression pattern</topic><topic>Head and Neck Neoplasms</topic><topic>Humans</topic><topic>immune microenvironment</topic><topic>Immune response</topic><topic>Immunohistochemistry</topic><topic>Interfaces</topic><topic>Localization</topic><topic>Mouth Neoplasms</topic><topic>Oral cancer</topic><topic>Oral carcinoma</topic><topic>Oral squamous cell carcinoma</topic><topic>PD-L1 protein</topic><topic>Prognosis</topic><topic>programmed cell death ligand 1</topic><topic>Retrospective Studies</topic><topic>Risk factors</topic><topic>score</topic><topic>Squamous cell carcinoma</topic><topic>Tumor cells</topic><topic>Tumor Microenvironment</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Miranda‐Galvis, Marisol</creatorcontrib><creatorcontrib>Rumayor Piña, Alicia</creatorcontrib><creatorcontrib>Sales de Sá, Raísa</creatorcontrib><creatorcontrib>Almeida Leite, Amanda</creatorcontrib><creatorcontrib>Agustin Vargas, Pablo</creatorcontrib><creatorcontrib>Calsavara, Vinicius Fernando</creatorcontrib><creatorcontrib>Lópes Pinto, Clóvis A.</creatorcontrib><creatorcontrib>Teng, Yong</creatorcontrib><creatorcontrib>Kowalski, Luiz Paulo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Oral diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miranda‐Galvis, Marisol</au><au>Rumayor Piña, Alicia</au><au>Sales de Sá, Raísa</au><au>Almeida Leite, Amanda</au><au>Agustin Vargas, Pablo</au><au>Calsavara, Vinicius Fernando</au><au>Lópes Pinto, Clóvis A.</au><au>Teng, Yong</au><au>Kowalski, Luiz Paulo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PD‐L1 expression patterns in oral cancer as an integrated approach for further prognostic classification</atitle><jtitle>Oral diseases</jtitle><addtitle>Oral Dis</addtitle><date>2021-10</date><risdate>2021</risdate><volume>27</volume><issue>7</issue><spage>1699</spage><epage>1710</epage><pages>1699-1710</pages><issn>1354-523X</issn><eissn>1601-0825</eissn><abstract>Background
Despite the well‐known role of programmed cell death ligand 1 (PD‐L1) in promoting immune resistance in oral squamous cell carcinoma (OSCC), its potential utility as a prognostic biomarker is undetermined. We evaluated PD‐L1 expression as predictor of survival in patients with OSCC and explored PD‐L1 expression patterns.
Methods
We conducted a retrospective cohort study that assessed PD‐L1 expression through immunohistochemistry in 123 surgical specimens of OSCC. A first approach evaluated tumor proportion scores (TPS) and combined proportion scores (CPS). Next, expression patterns were examined by evaluating PD‐L1 localization in tumor nests, as well as the interfaces of tumor cells (TC) and immune cells (IC) in the tumor microenvironment.
Results
High‐level PD‐L1 expression determined by TPS and CPS using variable cutoffs was not associated with survival. Immunohistochemistry revealed that TC expressed PD‐L1 in either patchy or diffuse patterns. The patchy pattern was an independent risk factor for overall survival. Furthermore, expression patterns in the tumor immune microenvironment showed that most cases expressed PD‐L1 on both TC and IC, while PD‐L1 non‐expressors had the lowest overall survival.
Conclusion
PD‐L1 expression patterns in the context of localization in tumor nests and TC—IC interactions represent antitumor immune responses better than either TPS or CPS. Our suggested classification system may have important implications for the characterization of OSCC and for the use of PD‐L1 as a prognostic biomarker.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>33169454</pmid><doi>10.1111/odi.13714</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-4798-584X</orcidid><orcidid>https://orcid.org/0000-0002-0481-156X</orcidid></addata></record> |
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subjects | Antitumor activity Apoptosis B7-H1 Antigen Biomarkers Carcinoma, Squamous Cell Cell death expression pattern Head and Neck Neoplasms Humans immune microenvironment Immune response Immunohistochemistry Interfaces Localization Mouth Neoplasms Oral cancer Oral carcinoma Oral squamous cell carcinoma PD-L1 protein Prognosis programmed cell death ligand 1 Retrospective Studies Risk factors score Squamous cell carcinoma Tumor cells Tumor Microenvironment |
title | PD‐L1 expression patterns in oral cancer as an integrated approach for further prognostic classification |
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