FOXP3 and CXCR4-positive regulatory T cells in the tumor stroma as indicators of tumor immunity in the conjunctival squamous cell carcinoma microenvironment
Conjunctival squamous cell carcinoma (SCC) is the most common ocular surface neoplasia. The purpose of this retrospective study was to examine the role of regulatory T cell (Treg) activity in tumor immunity and investigate the tumor microenvironment as a new treatment focus in conjunctival SCC. Canc...
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| creator | Tagami, Mizuki Kakehashi, Anna Katsuyama-Yoshikawa, Atsuko Misawa, Norihiko Sakai, Atsushi Wanibuchi, Hideki Azumi, Atsushi Honda, Shigeru |
| description | Conjunctival squamous cell carcinoma (SCC) is the most common ocular surface neoplasia. The purpose of this retrospective study was to examine the role of regulatory T cell (Treg) activity in tumor immunity and investigate the tumor microenvironment as a new treatment focus in conjunctival SCC. Cancer progression gene array and immunohistochemical analyses of FOXP3 as a Treg marker, CD8 as a tumor-infiltrating lymphocyte marker, and CXCR4 expression on activated Tregs were conducted in a series of 31 conjunctival SCC cases. The objective was to investigate the immunoreactive response in tumor cells and stromal cells in the cancer microenvironment. The stroma ratio in tumor cells was investigated by monitoring α-smooth muscle actine (SMA) expression between carcinoma in situ (Tis) and advanced carcinoma (Tadv) (P |
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The purpose of this retrospective study was to examine the role of regulatory T cell (Treg) activity in tumor immunity and investigate the tumor microenvironment as a new treatment focus in conjunctival SCC. Cancer progression gene array and immunohistochemical analyses of FOXP3 as a Treg marker, CD8 as a tumor-infiltrating lymphocyte marker, and CXCR4 expression on activated Tregs were conducted in a series of 31 conjunctival SCC cases. The objective was to investigate the immunoreactive response in tumor cells and stromal cells in the cancer microenvironment. The stroma ratio in tumor cells was investigated by monitoring α-smooth muscle actine (SMA) expression between carcinoma in situ (Tis) and advanced carcinoma (Tadv) (P<0.01). No significant change in PD-L1 expression was observed in this study (P = 0.15). Staining patterns of FOXP3, CD8, and CXCR4 were examined separately between tumor cells and stromal cells in SCC tumors. Differences in staining of FOXP3 in Tregs and CD8 in tumor-infiltrating lymphocytes in tumor stroma in the Tis group were observed compared with the Tadv group (each P<0.01). In addition, double immunostaining of CXCR4/FOXP3 was correlated with progression-free survival (P = 0.049). Double immunostaining of CXCR4/FOXP3 correlated with American Joint Committee on Cancer T-stage, independent of age or Ki67 index (P<0.01). Our results show that FOXP3 and the CXCR4/FOXP3 axis are important pathologic and prognostic factors of ocular surface neoplasia, including SCC. The tumor microenvironment of conjunctival SCC should be considered in the future development of treatment options.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0263895</identifier><identifier>PMID: 35358193</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Apoptosis ; Biology and life sciences ; Cancer ; Carcinoma, Squamous Cell - immunology ; Care and treatment ; CD8 antigen ; CD8-Positive T-Lymphocytes ; Cloning ; Conjunctival Neoplasms - immunology ; CXCR4 protein ; Forkhead Transcription Factors - metabolism ; Foxp3 protein ; Gene expression ; Genetic aspects ; Health aspects ; Hospitals ; Humans ; Immunity ; Immunoregulation ; Laboratories ; Lymphocytes ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating ; Markers ; Medicine ; Medicine and Health Sciences ; Muscles ; Ophthalmology ; Pathology ; PD-L1 protein ; Prognosis ; Receptors, CXCR4 - metabolism ; Research and Analysis Methods ; Retrospective Studies ; Smooth muscle ; Squamous cell carcinoma ; Staining ; Stromal cells ; T cells ; T-Lymphocytes, Regulatory ; Tumor cells ; Tumor Microenvironment ; Tumor-infiltrating lymphocytes ; Tumors</subject><ispartof>PloS one, 2022-03, Vol.17 (3), p.e0263895-e0263895</ispartof><rights>COPYRIGHT 2022 Public Library of Science</rights><rights>2022 Tagami et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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The purpose of this retrospective study was to examine the role of regulatory T cell (Treg) activity in tumor immunity and investigate the tumor microenvironment as a new treatment focus in conjunctival SCC. Cancer progression gene array and immunohistochemical analyses of FOXP3 as a Treg marker, CD8 as a tumor-infiltrating lymphocyte marker, and CXCR4 expression on activated Tregs were conducted in a series of 31 conjunctival SCC cases. The objective was to investigate the immunoreactive response in tumor cells and stromal cells in the cancer microenvironment. The stroma ratio in tumor cells was investigated by monitoring α-smooth muscle actine (SMA) expression between carcinoma in situ (Tis) and advanced carcinoma (Tadv) (P<0.01). No significant change in PD-L1 expression was observed in this study (P = 0.15). Staining patterns of FOXP3, CD8, and CXCR4 were examined separately between tumor cells and stromal cells in SCC tumors. Differences in staining of FOXP3 in Tregs and CD8 in tumor-infiltrating lymphocytes in tumor stroma in the Tis group were observed compared with the Tadv group (each P<0.01). In addition, double immunostaining of CXCR4/FOXP3 was correlated with progression-free survival (P = 0.049). Double immunostaining of CXCR4/FOXP3 correlated with American Joint Committee on Cancer T-stage, independent of age or Ki67 index (P<0.01). Our results show that FOXP3 and the CXCR4/FOXP3 axis are important pathologic and prognostic factors of ocular surface neoplasia, including SCC. The tumor microenvironment of conjunctival SCC should be considered in the future development of treatment options.</description><subject>Apoptosis</subject><subject>Biology and life sciences</subject><subject>Cancer</subject><subject>Carcinoma, Squamous Cell - immunology</subject><subject>Care and treatment</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes</subject><subject>Cloning</subject><subject>Conjunctival Neoplasms - immunology</subject><subject>CXCR4 protein</subject><subject>Forkhead Transcription Factors - metabolism</subject><subject>Foxp3 protein</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunity</subject><subject>Immunoregulation</subject><subject>Laboratories</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Lymphocytes, Tumor-Infiltrating</subject><subject>Markers</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Muscles</subject><subject>Ophthalmology</subject><subject>Pathology</subject><subject>PD-L1 protein</subject><subject>Prognosis</subject><subject>Receptors, CXCR4 - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tagami, Mizuki</au><au>Kakehashi, Anna</au><au>Katsuyama-Yoshikawa, Atsuko</au><au>Misawa, Norihiko</au><au>Sakai, Atsushi</au><au>Wanibuchi, Hideki</au><au>Azumi, Atsushi</au><au>Honda, Shigeru</au><au>Raza, Afsheen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>FOXP3 and CXCR4-positive regulatory T cells in the tumor stroma as indicators of tumor immunity in the conjunctival squamous cell carcinoma microenvironment</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2022-03-31</date><risdate>2022</risdate><volume>17</volume><issue>3</issue><spage>e0263895</spage><epage>e0263895</epage><pages>e0263895-e0263895</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Conjunctival squamous cell carcinoma (SCC) is the most common ocular surface neoplasia. The purpose of this retrospective study was to examine the role of regulatory T cell (Treg) activity in tumor immunity and investigate the tumor microenvironment as a new treatment focus in conjunctival SCC. Cancer progression gene array and immunohistochemical analyses of FOXP3 as a Treg marker, CD8 as a tumor-infiltrating lymphocyte marker, and CXCR4 expression on activated Tregs were conducted in a series of 31 conjunctival SCC cases. The objective was to investigate the immunoreactive response in tumor cells and stromal cells in the cancer microenvironment. The stroma ratio in tumor cells was investigated by monitoring α-smooth muscle actine (SMA) expression between carcinoma in situ (Tis) and advanced carcinoma (Tadv) (P<0.01). No significant change in PD-L1 expression was observed in this study (P = 0.15). Staining patterns of FOXP3, CD8, and CXCR4 were examined separately between tumor cells and stromal cells in SCC tumors. Differences in staining of FOXP3 in Tregs and CD8 in tumor-infiltrating lymphocytes in tumor stroma in the Tis group were observed compared with the Tadv group (each P<0.01). In addition, double immunostaining of CXCR4/FOXP3 was correlated with progression-free survival (P = 0.049). Double immunostaining of CXCR4/FOXP3 correlated with American Joint Committee on Cancer T-stage, independent of age or Ki67 index (P<0.01). Our results show that FOXP3 and the CXCR4/FOXP3 axis are important pathologic and prognostic factors of ocular surface neoplasia, including SCC. The tumor microenvironment of conjunctival SCC should be considered in the future development of treatment options.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>35358193</pmid><doi>10.1371/journal.pone.0263895</doi><tpages>e0263895</tpages><orcidid>https://orcid.org/0000-0003-1149-1450</orcidid><orcidid>https://orcid.org/0000-0002-8771-7252</orcidid><orcidid>https://orcid.org/0000-0001-8399-6082</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Apoptosis Biology and life sciences Cancer Carcinoma, Squamous Cell - immunology Care and treatment CD8 antigen CD8-Positive T-Lymphocytes Cloning Conjunctival Neoplasms - immunology CXCR4 protein Forkhead Transcription Factors - metabolism Foxp3 protein Gene expression Genetic aspects Health aspects Hospitals Humans Immunity Immunoregulation Laboratories Lymphocytes Lymphocytes T Lymphocytes, Tumor-Infiltrating Markers Medicine Medicine and Health Sciences Muscles Ophthalmology Pathology PD-L1 protein Prognosis Receptors, CXCR4 - metabolism Research and Analysis Methods Retrospective Studies Smooth muscle Squamous cell carcinoma Staining Stromal cells T cells T-Lymphocytes, Regulatory Tumor cells Tumor Microenvironment Tumor-infiltrating lymphocytes Tumors |
| title | FOXP3 and CXCR4-positive regulatory T cells in the tumor stroma as indicators of tumor immunity in the conjunctival squamous cell carcinoma microenvironment |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T22%3A04%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=FOXP3%20and%20CXCR4-positive%20regulatory%20T%20cells%20in%20the%20tumor%20stroma%20as%20indicators%20of%20tumor%20immunity%20in%20the%20conjunctival%20squamous%20cell%20carcinoma%20microenvironment&rft.jtitle=PloS%20one&rft.au=Tagami,%20Mizuki&rft.date=2022-03-31&rft.volume=17&rft.issue=3&rft.spage=e0263895&rft.epage=e0263895&rft.pages=e0263895-e0263895&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0263895&rft_dat=%3Cgale_plos_%3EA698926215%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2645867268&rft_id=info:pmid/35358193&rft_galeid=A698926215&rft_doaj_id=oai_doaj_org_article_bc389eb2de36440bb4a29b888cff96b6&rfr_iscdi=true |