Impact of T Cell Ratios on Survival in Pleural Mesothelioma: Insights from Tumor Microenvironment Analysis
Immunotherapy has significantly improved overall survival in patients with pleural mesothelioma, yet this benefit does not extend to those with the epithelioid subtype. Tumor growth is believed to be influenced by the immune response. This study aimed to analyze the tumor microenvironment to gain a...
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| Veröffentlicht in: | Cancers 2024-10, Vol.16 (19), p.3418 |
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| creator | Klotz, Laura V Weigert, Andreas Eichhorn, Florian Allgäuer, Michael Muley, Thomas Shah, Rajiv Savai, Rajkumar Eichhorn, Martin E Winter, Hauke |
| description | Immunotherapy has significantly improved overall survival in patients with pleural mesothelioma, yet this benefit does not extend to those with the epithelioid subtype. Tumor growth is believed to be influenced by the immune response. This study aimed to analyze the tumor microenvironment to gain a better understanding of its influence on tumor growth.
The tumor immune cell infiltration of 188 patients with pleural mesothelioma was characterized by multiplex immunofluorescence staining for CD3+ cells (CD3+), CD4+ cells (CD3+/CD4+), CD8+ cells (CD3+/CD8+), Treg (CD3+/CD4+/CD8-/CD163-/Foxp3+), PD1 cells (PD1+), and T helper cells (CD3+/CD4+/CD8-/CD163-/FoxP3-). The distribution of specific immune cells was correlated with clinical parameters.
A total of 188 patients with pleural mesothelioma (135 epithelioid, 9 sarcomatoid, 44 biphasic subtypes) were analyzed. The median age was 64.8 years. Overall survival was significantly longer in the epithelioid subtype than in the non-epithelioid subtype (
= 0.016). The presence of PD-L1 expression had a negative effect on overall survival (
= 0.041). A high ratio of CD4+ cells to regulatory T cells was associated with a significantly longer overall survival of more than 12 months (
= 0.015). The ratio of CD4+ cells to regulatory T cells retained its significant effect on overall survival in the multivariate analysis.
Distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival. The tumor microenvironment could therefore serve as a source of prognostic biomarkers. |
| doi_str_mv | 10.3390/cancers16193418 |
| format | Article |
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The tumor immune cell infiltration of 188 patients with pleural mesothelioma was characterized by multiplex immunofluorescence staining for CD3+ cells (CD3+), CD4+ cells (CD3+/CD4+), CD8+ cells (CD3+/CD8+), Treg (CD3+/CD4+/CD8-/CD163-/Foxp3+), PD1 cells (PD1+), and T helper cells (CD3+/CD4+/CD8-/CD163-/FoxP3-). The distribution of specific immune cells was correlated with clinical parameters.
A total of 188 patients with pleural mesothelioma (135 epithelioid, 9 sarcomatoid, 44 biphasic subtypes) were analyzed. The median age was 64.8 years. Overall survival was significantly longer in the epithelioid subtype than in the non-epithelioid subtype (
= 0.016). The presence of PD-L1 expression had a negative effect on overall survival (
= 0.041). A high ratio of CD4+ cells to regulatory T cells was associated with a significantly longer overall survival of more than 12 months (
= 0.015). The ratio of CD4+ cells to regulatory T cells retained its significant effect on overall survival in the multivariate analysis.
Distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival. The tumor microenvironment could therefore serve as a source of prognostic biomarkers.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers16193418</identifier><identifier>PMID: 39410037</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Automation ; Biomarkers ; Biopsy ; Care and treatment ; CD163 antigen ; CD3 antigen ; CD4 antigen ; CD8 antigen ; Chemotherapy ; Disease ; Drug therapy ; Foxp3 protein ; Health aspects ; Helper cells ; Histology ; Immunofluorescence ; Immunoregulation ; Immunotherapy ; Lymphocytes ; Lymphocytes T ; Measurement ; Mesothelioma ; Metastases ; Multivariate analysis ; Patient outcomes ; Patients ; PD-1 protein ; PD-L1 protein ; Pleural diseases ; Prognosis ; Software ; Survival analysis ; T cells ; Thoracic surgery ; Tumor microenvironment ; Tumor-infiltrating lymphocytes ; Tumors</subject><ispartof>Cancers, 2024-10, Vol.16 (19), p.3418</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-c373t-ab6f447a21ccf2233edcbbef13cb7c6674dac004fd16589a725cdb846cf076e73</cites><orcidid>0000-0002-1543-9281 ; 0000-0002-8141-0604 ; 0000-0003-1538-2091 ; 0000-0003-4518-7887 ; 0000-0002-7529-1952</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/PMC11476058/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476058/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39410037$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Klotz, Laura V</creatorcontrib><creatorcontrib>Weigert, Andreas</creatorcontrib><creatorcontrib>Eichhorn, Florian</creatorcontrib><creatorcontrib>Allgäuer, Michael</creatorcontrib><creatorcontrib>Muley, Thomas</creatorcontrib><creatorcontrib>Shah, Rajiv</creatorcontrib><creatorcontrib>Savai, Rajkumar</creatorcontrib><creatorcontrib>Eichhorn, Martin E</creatorcontrib><creatorcontrib>Winter, Hauke</creatorcontrib><title>Impact of T Cell Ratios on Survival in Pleural Mesothelioma: Insights from Tumor Microenvironment Analysis</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>Immunotherapy has significantly improved overall survival in patients with pleural mesothelioma, yet this benefit does not extend to those with the epithelioid subtype. Tumor growth is believed to be influenced by the immune response. This study aimed to analyze the tumor microenvironment to gain a better understanding of its influence on tumor growth.
The tumor immune cell infiltration of 188 patients with pleural mesothelioma was characterized by multiplex immunofluorescence staining for CD3+ cells (CD3+), CD4+ cells (CD3+/CD4+), CD8+ cells (CD3+/CD8+), Treg (CD3+/CD4+/CD8-/CD163-/Foxp3+), PD1 cells (PD1+), and T helper cells (CD3+/CD4+/CD8-/CD163-/FoxP3-). The distribution of specific immune cells was correlated with clinical parameters.
A total of 188 patients with pleural mesothelioma (135 epithelioid, 9 sarcomatoid, 44 biphasic subtypes) were analyzed. The median age was 64.8 years. Overall survival was significantly longer in the epithelioid subtype than in the non-epithelioid subtype (
= 0.016). The presence of PD-L1 expression had a negative effect on overall survival (
= 0.041). A high ratio of CD4+ cells to regulatory T cells was associated with a significantly longer overall survival of more than 12 months (
= 0.015). The ratio of CD4+ cells to regulatory T cells retained its significant effect on overall survival in the multivariate analysis.
Distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival. The tumor microenvironment could therefore serve as a source of prognostic biomarkers.</description><subject>Automation</subject><subject>Biomarkers</subject><subject>Biopsy</subject><subject>Care and treatment</subject><subject>CD163 antigen</subject><subject>CD3 antigen</subject><subject>CD4 antigen</subject><subject>CD8 antigen</subject><subject>Chemotherapy</subject><subject>Disease</subject><subject>Drug therapy</subject><subject>Foxp3 protein</subject><subject>Health aspects</subject><subject>Helper cells</subject><subject>Histology</subject><subject>Immunofluorescence</subject><subject>Immunoregulation</subject><subject>Immunotherapy</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Measurement</subject><subject>Mesothelioma</subject><subject>Metastases</subject><subject>Multivariate analysis</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>PD-1 protein</subject><subject>PD-L1 protein</subject><subject>Pleural diseases</subject><subject>Prognosis</subject><subject>Software</subject><subject>Survival analysis</subject><subject>T cells</subject><subject>Thoracic surgery</subject><subject>Tumor microenvironment</subject><subject>Tumor-infiltrating lymphocytes</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNptUk1vGyEQRVWrJkpzzq1C6qUXJ7CwsNtLZVltYylRotY5I5YdbKwFXNi1lH9f8tE0iQoHBnjvzczTIHRCySljLTkzOhhImQraMk6bN-iwIrKaCdHyt8_iA3Sc85aUxRiVQr5HB6zltFzlIdou_U6bEUeLV3gBw4B_6tHFjGPAv6a0d3s9YBfw9QBTKuEl5DhuYHDR6y94GbJbb8aMbYoeryYfE750JkUIe5di8BBGPA96uM0uf0DvrB4yHD-eR-jm-7fV4nx2cfVjuZhfzAyTbJzpTljOpa6oMbaqGIPedB1YykwnjRCS99oQwm1PRd20Wla16buGC2OJFCDZEfr6oLubOl_IpYZSudol53W6VVE79fInuI1ax72ilEtB6qYofH5USPH3BHlU3mVTzNEB4pQVo1QSKYudBfrpFXQbp1Q6vkeJWnJWy3-otR5AuWBjSWzuRNW8oZWgvOZtQZ3-B1V2D96ZGMC68v6CcPZAKI7nnMA-NUmJuhsR9WpECuPjc2-e8H8Hgv0BsVW4xA</recordid><startdate>20241008</startdate><enddate>20241008</enddate><creator>Klotz, Laura V</creator><creator>Weigert, Andreas</creator><creator>Eichhorn, Florian</creator><creator>Allgäuer, Michael</creator><creator>Muley, Thomas</creator><creator>Shah, Rajiv</creator><creator>Savai, Rajkumar</creator><creator>Eichhorn, Martin E</creator><creator>Winter, Hauke</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</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>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1543-9281</orcidid><orcidid>https://orcid.org/0000-0002-8141-0604</orcidid><orcidid>https://orcid.org/0000-0003-1538-2091</orcidid><orcidid>https://orcid.org/0000-0003-4518-7887</orcidid><orcidid>https://orcid.org/0000-0002-7529-1952</orcidid></search><sort><creationdate>20241008</creationdate><title>Impact of T Cell Ratios on Survival in Pleural Mesothelioma: Insights from Tumor Microenvironment Analysis</title><author>Klotz, Laura V ; 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Tumor growth is believed to be influenced by the immune response. This study aimed to analyze the tumor microenvironment to gain a better understanding of its influence on tumor growth.
The tumor immune cell infiltration of 188 patients with pleural mesothelioma was characterized by multiplex immunofluorescence staining for CD3+ cells (CD3+), CD4+ cells (CD3+/CD4+), CD8+ cells (CD3+/CD8+), Treg (CD3+/CD4+/CD8-/CD163-/Foxp3+), PD1 cells (PD1+), and T helper cells (CD3+/CD4+/CD8-/CD163-/FoxP3-). The distribution of specific immune cells was correlated with clinical parameters.
A total of 188 patients with pleural mesothelioma (135 epithelioid, 9 sarcomatoid, 44 biphasic subtypes) were analyzed. The median age was 64.8 years. Overall survival was significantly longer in the epithelioid subtype than in the non-epithelioid subtype (
= 0.016). The presence of PD-L1 expression had a negative effect on overall survival (
= 0.041). A high ratio of CD4+ cells to regulatory T cells was associated with a significantly longer overall survival of more than 12 months (
= 0.015). The ratio of CD4+ cells to regulatory T cells retained its significant effect on overall survival in the multivariate analysis.
Distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival. The tumor microenvironment could therefore serve as a source of prognostic biomarkers.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>39410037</pmid><doi>10.3390/cancers16193418</doi><orcidid>https://orcid.org/0000-0002-1543-9281</orcidid><orcidid>https://orcid.org/0000-0002-8141-0604</orcidid><orcidid>https://orcid.org/0000-0003-1538-2091</orcidid><orcidid>https://orcid.org/0000-0003-4518-7887</orcidid><orcidid>https://orcid.org/0000-0002-7529-1952</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Automation Biomarkers Biopsy Care and treatment CD163 antigen CD3 antigen CD4 antigen CD8 antigen Chemotherapy Disease Drug therapy Foxp3 protein Health aspects Helper cells Histology Immunofluorescence Immunoregulation Immunotherapy Lymphocytes Lymphocytes T Measurement Mesothelioma Metastases Multivariate analysis Patient outcomes Patients PD-1 protein PD-L1 protein Pleural diseases Prognosis Software Survival analysis T cells Thoracic surgery Tumor microenvironment Tumor-infiltrating lymphocytes Tumors |
| title | Impact of T Cell Ratios on Survival in Pleural Mesothelioma: Insights from Tumor Microenvironment Analysis |
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