The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study
Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expr...
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| Veröffentlicht in: | Cancers 2024-06, Vol.16 (11), p.2140 |
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| creator | Asakawa, Ayaka Yoshimoto, Ryoto Kobayashi, Maki Izumi, Nanae Maejima, Takanori Deguchi, Tsuneo Kubota, Kazuishi Takahashi, Hisashi Yamada, Miyuki Ishibashi, Sachiko Onishi, Iichiroh Kinowaki, Yuko Kurata, Morito Kobayashi, Masashi Ishibashi, Hironori Okubo, Kenichi Ohashi, Kenichi Kitagawa, Masanobu Yamamoto, Kouhei |
| description | Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated in detail. We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME. We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression using 110 surgically resected pathological specimens retrospectively. We examined the correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells. High B7-H3 expression in tumor cells was associated with a better prognosis and a significant increase in the number of CD163
PD-L1
macrophages. Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68
, CD163
, and CK
cells with PD-L1
phenotypes had higher B7-H3 expression compared to PD-L1
cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies. |
| doi_str_mv | 10.3390/cancers16112140 |
| format | Article |
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PD-L1
macrophages. Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68
, CD163
, and CK
cells with PD-L1
phenotypes had higher B7-H3 expression compared to PD-L1
cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers16112140</identifier><identifier>PMID: 38893259</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Antibodies ; Apoptosis ; Automation ; Cancer therapies ; CD163 antigen ; Cell death ; Cells ; Development and progression ; Genetic aspects ; Health aspects ; Immune checkpoint ; Immunohistochemistry ; Immunotherapy ; Lung cancer ; Lung carcinoma ; Lymphocytes ; Macrophages ; Measurement ; Medical prognosis ; Membrane proteins ; Pathology ; Patients ; PD-L1 protein ; Phenotypes ; Prognosis ; Software ; Squamous cell carcinoma ; Stromal cells ; Tumor cells ; Tumor microenvironment ; Tumor-infiltrating lymphocytes</subject><ispartof>Cancers, 2024-06, Vol.16 (11), p.2140</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 by the authors. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c443t-331d3bed495140cb597c7c379c7832ab891cfa6631327e51a32f005beb99030c3</cites><orcidid>0000-0002-1450-0589 ; 0000-0003-3883-4353 ; 0000-0001-6817-1613 ; 0000-0002-4628-2408 ; 0000-0001-9744-0114 ; 0000-0002-1242-6709 ; 0000-0001-5920-5906 ; 0000-0001-8907-2569</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11171371/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11171371/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38893259$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Asakawa, Ayaka</creatorcontrib><creatorcontrib>Yoshimoto, Ryoto</creatorcontrib><creatorcontrib>Kobayashi, Maki</creatorcontrib><creatorcontrib>Izumi, Nanae</creatorcontrib><creatorcontrib>Maejima, Takanori</creatorcontrib><creatorcontrib>Deguchi, Tsuneo</creatorcontrib><creatorcontrib>Kubota, Kazuishi</creatorcontrib><creatorcontrib>Takahashi, Hisashi</creatorcontrib><creatorcontrib>Yamada, Miyuki</creatorcontrib><creatorcontrib>Ishibashi, Sachiko</creatorcontrib><creatorcontrib>Onishi, Iichiroh</creatorcontrib><creatorcontrib>Kinowaki, Yuko</creatorcontrib><creatorcontrib>Kurata, Morito</creatorcontrib><creatorcontrib>Kobayashi, Masashi</creatorcontrib><creatorcontrib>Ishibashi, Hironori</creatorcontrib><creatorcontrib>Okubo, Kenichi</creatorcontrib><creatorcontrib>Ohashi, Kenichi</creatorcontrib><creatorcontrib>Kitagawa, Masanobu</creatorcontrib><creatorcontrib>Yamamoto, Kouhei</creatorcontrib><title>The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated in detail. We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME. We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression using 110 surgically resected pathological specimens retrospectively. We examined the correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells. High B7-H3 expression in tumor cells was associated with a better prognosis and a significant increase in the number of CD163
PD-L1
macrophages. Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68
, CD163
, and CK
cells with PD-L1
phenotypes had higher B7-H3 expression compared to PD-L1
cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies.</description><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Automation</subject><subject>Cancer therapies</subject><subject>CD163 antigen</subject><subject>Cell death</subject><subject>Cells</subject><subject>Development and progression</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Immune checkpoint</subject><subject>Immunohistochemistry</subject><subject>Immunotherapy</subject><subject>Lung cancer</subject><subject>Lung carcinoma</subject><subject>Lymphocytes</subject><subject>Macrophages</subject><subject>Measurement</subject><subject>Medical prognosis</subject><subject>Membrane proteins</subject><subject>Pathology</subject><subject>Patients</subject><subject>PD-L1 protein</subject><subject>Phenotypes</subject><subject>Prognosis</subject><subject>Software</subject><subject>Squamous cell carcinoma</subject><subject>Stromal cells</subject><subject>Tumor cells</subject><subject>Tumor microenvironment</subject><subject>Tumor-infiltrating 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Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study</title><author>Asakawa, Ayaka ; Yoshimoto, Ryoto ; Kobayashi, Maki ; Izumi, Nanae ; Maejima, Takanori ; Deguchi, Tsuneo ; Kubota, Kazuishi ; Takahashi, Hisashi ; Yamada, Miyuki ; Ishibashi, Sachiko ; Onishi, Iichiroh ; Kinowaki, Yuko ; Kurata, Morito ; Kobayashi, Masashi ; Ishibashi, Hironori ; Okubo, Kenichi ; Ohashi, Kenichi ; Kitagawa, Masanobu ; Yamamoto, Kouhei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c443t-331d3bed495140cb597c7c379c7832ab891cfa6631327e51a32f005beb99030c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Automation</topic><topic>Cancer therapies</topic><topic>CD163 antigen</topic><topic>Cell death</topic><topic>Cells</topic><topic>Development and progression</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Immune checkpoint</topic><topic>Immunohistochemistry</topic><topic>Immunotherapy</topic><topic>Lung cancer</topic><topic>Lung carcinoma</topic><topic>Lymphocytes</topic><topic>Macrophages</topic><topic>Measurement</topic><topic>Medical prognosis</topic><topic>Membrane proteins</topic><topic>Pathology</topic><topic>Patients</topic><topic>PD-L1 protein</topic><topic>Phenotypes</topic><topic>Prognosis</topic><topic>Software</topic><topic>Squamous cell carcinoma</topic><topic>Stromal cells</topic><topic>Tumor cells</topic><topic>Tumor microenvironment</topic><topic>Tumor-infiltrating lymphocytes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Asakawa, Ayaka</creatorcontrib><creatorcontrib>Yoshimoto, Ryoto</creatorcontrib><creatorcontrib>Kobayashi, Maki</creatorcontrib><creatorcontrib>Izumi, Nanae</creatorcontrib><creatorcontrib>Maejima, 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Yuko</au><au>Kurata, Morito</au><au>Kobayashi, Masashi</au><au>Ishibashi, Hironori</au><au>Okubo, Kenichi</au><au>Ohashi, Kenichi</au><au>Kitagawa, Masanobu</au><au>Yamamoto, Kouhei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2024-06-04</date><risdate>2024</risdate><volume>16</volume><issue>11</issue><spage>2140</spage><pages>2140-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Lung squamous cell carcinoma (LSCC) is refractory to various therapies for non-small cell cancer; therefore, new therapeutic approaches are required to improve the prognosis of LSCC. Although immunotherapies targeting B7 family molecules were explored as treatments for several cancer types, the expression and significance of B7-H3 in the tumor microenvironment (TME) and its relationship with other immune checkpoint molecules have not yet been investigated in detail. We used high-throughput quantitative multiplex immunohistochemistry to examine B7-H3 expression in the TME. We investigated the relationship between B7-H3 expression and prognosis as well as changes in the TME with B7-H3 expression using 110 surgically resected pathological specimens retrospectively. We examined the correlation between B7-H3 and programmed cell death-ligand 1 (PD-L1) expression in single cells. High B7-H3 expression in tumor cells was associated with a better prognosis and a significant increase in the number of CD163
PD-L1
macrophages. Quantitative analysis revealed that there is a positive correlation between B7-H3 and PD-L1 expression in tumor and stromal cells, as well as in intratumoral tumor-infiltrating lymphocytes and tumor-associated macrophages in the same cells. CD68
, CD163
, and CK
cells with PD-L1
phenotypes had higher B7-H3 expression compared to PD-L1
cells. Our findings demonstrate a correlation between B7-H3 and PD-L1 expression in the same cells, indicating that therapies targeting B7-H3 could provide additional efficacy in patients refractory to PD-L1-targeting therapies.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>38893259</pmid><doi>10.3390/cancers16112140</doi><orcidid>https://orcid.org/0000-0002-1450-0589</orcidid><orcidid>https://orcid.org/0000-0003-3883-4353</orcidid><orcidid>https://orcid.org/0000-0001-6817-1613</orcidid><orcidid>https://orcid.org/0000-0002-4628-2408</orcidid><orcidid>https://orcid.org/0000-0001-9744-0114</orcidid><orcidid>https://orcid.org/0000-0002-1242-6709</orcidid><orcidid>https://orcid.org/0000-0001-5920-5906</orcidid><orcidid>https://orcid.org/0000-0001-8907-2569</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2072-6694 |
| ispartof | Cancers, 2024-06, Vol.16 (11), p.2140 |
| issn | 2072-6694 2072-6694 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11171371 |
| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Antibodies Apoptosis Automation Cancer therapies CD163 antigen Cell death Cells Development and progression Genetic aspects Health aspects Immune checkpoint Immunohistochemistry Immunotherapy Lung cancer Lung carcinoma Lymphocytes Macrophages Measurement Medical prognosis Membrane proteins Pathology Patients PD-L1 protein Phenotypes Prognosis Software Squamous cell carcinoma Stromal cells Tumor cells Tumor microenvironment Tumor-infiltrating lymphocytes |
| title | The Comprehensive Characterization of B7-H3 Expression in the Tumor Microenvironment of Lung Squamous Cell Carcinoma: A Retrospective Study |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T05%3A21%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20Comprehensive%20Characterization%20of%20B7-H3%20Expression%20in%20the%20Tumor%20Microenvironment%20of%20Lung%20Squamous%20Cell%20Carcinoma:%20A%20Retrospective%20Study&rft.jtitle=Cancers&rft.au=Asakawa,%20Ayaka&rft.date=2024-06-04&rft.volume=16&rft.issue=11&rft.spage=2140&rft.pages=2140-&rft.issn=2072-6694&rft.eissn=2072-6694&rft_id=info:doi/10.3390/cancers16112140&rft_dat=%3Cgale_pubme%3EA797899157%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3067385038&rft_id=info:pmid/38893259&rft_galeid=A797899157&rfr_iscdi=true |