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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
Main Authors: 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
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container_end_page 1710
container_issue 7
container_start_page 1699
container_title Oral diseases
container_volume 27
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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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 &amp; Sons A/S. Published by John Wiley &amp; 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. 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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 &amp; Calcified Tissue Abstracts</collection><collection>ProQuest Health &amp; 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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