David Dora, Zsolt Megyesfalvi, Imre Vörös, Ágnes Paál, Peter Takacs, Daniela Dobos, Bence Lőrincz, Syeda Mahak Zahra Bokhari, Kenan Aloss, Gergely Pallag, Christopher Rivard, Hui Yu, Fred R Hirsch, Anikó Görbe, Zoltán V Varga, Zoltan Lohinai, Balazs Dome
{"title":"共刺激分子CD70的表达与小细胞肺癌的预后有关。","authors":"David Dora, Zsolt Megyesfalvi, Imre Vörös, Ágnes Paál, Peter Takacs, Daniela Dobos, Bence Lőrincz, Syeda Mahak Zahra Bokhari, Kenan Aloss, Gergely Pallag, Christopher Rivard, Hui Yu, Fred R Hirsch, Anikó Görbe, Zoltán V Varga, Zoltan Lohinai, Balazs Dome","doi":"10.1007/s00262-025-04006-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor survival outcomes. The CD70-CD27 axis has been implicated in immune regulation and tumor progression across cancers, but its role in SCLC has not yet been elucidated. This research explores the expression patterns and prognostic significance of CD70 and CD27 in early-stage SCLC.</p><p><strong>Methods: </strong>In this retrospective study, we analyzed 190 surgically resected SCLC tumor samples using immunohistochemistry (IHC) for CD70 and CD27 expression and RNAscope for CD70 RNA detection. Immune infiltration was assessed using CD45, CD8, and CD20 staining. Quantification of RNAscope signals was performed using QPath software. Kaplan-Meier survival analysis and multivariate Cox regression were used to assess the prognostic impact of CD70, CD27, and immune cell infiltrates on overall survival (OS).</p><p><strong>Results: </strong>CD70 was expressed in 46% of tumors, primarily within tumor nests, with lower expression in stromal areas. High CD70 expression correlated with significantly decreased OS (p = 0.0078, HR: 1.795) without any correlation with CD45 + , CD8 + or CD20 + immune cell infiltrates. CD27 expression was mainly confined to the stroma, and it did not show a significant association with OS (p = 0.582). Importantly, high CD27 expression was linked to reduced CD45 + and CD8 + cell densities in the stroma. Both CD70 and CD27 were expressed on CD68 + macrophages, CD27 was expressed on CAFs, and both molecules exhibited a partial coexpression with CD3. Furthermore, patients with high CD20 + B-cell densities or the presence of tertiary lymphoid structures (TLS) had significantly improved OS (p = 0.0017, HR: 0.491), suggesting the importance of B-cell-related immune responses in SCLC prognosis.</p><p><strong>Conclusion: </strong>CD70, B-cell density and the presence of TLSs, but not CD27, emerged as a significant prognostic biomarker for OS in surgically treated SCLC, suggesting its potential as a therapeutic target.</p>","PeriodicalId":9595,"journal":{"name":"Cancer Immunology, Immunotherapy","volume":"74 5","pages":"165"},"PeriodicalIF":5.1000,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11981989/pdf/","citationCount":"0","resultStr":"{\"title\":\"Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer.\",\"authors\":\"David Dora, Zsolt Megyesfalvi, Imre Vörös, Ágnes Paál, Peter Takacs, Daniela Dobos, Bence Lőrincz, Syeda Mahak Zahra Bokhari, Kenan Aloss, Gergely Pallag, Christopher Rivard, Hui Yu, Fred R Hirsch, Anikó Görbe, Zoltán V Varga, Zoltan Lohinai, Balazs Dome\",\"doi\":\"10.1007/s00262-025-04006-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor survival outcomes. The CD70-CD27 axis has been implicated in immune regulation and tumor progression across cancers, but its role in SCLC has not yet been elucidated. This research explores the expression patterns and prognostic significance of CD70 and CD27 in early-stage SCLC.</p><p><strong>Methods: </strong>In this retrospective study, we analyzed 190 surgically resected SCLC tumor samples using immunohistochemistry (IHC) for CD70 and CD27 expression and RNAscope for CD70 RNA detection. Immune infiltration was assessed using CD45, CD8, and CD20 staining. Quantification of RNAscope signals was performed using QPath software. Kaplan-Meier survival analysis and multivariate Cox regression were used to assess the prognostic impact of CD70, CD27, and immune cell infiltrates on overall survival (OS).</p><p><strong>Results: </strong>CD70 was expressed in 46% of tumors, primarily within tumor nests, with lower expression in stromal areas. High CD70 expression correlated with significantly decreased OS (p = 0.0078, HR: 1.795) without any correlation with CD45 + , CD8 + or CD20 + immune cell infiltrates. CD27 expression was mainly confined to the stroma, and it did not show a significant association with OS (p = 0.582). Importantly, high CD27 expression was linked to reduced CD45 + and CD8 + cell densities in the stroma. Both CD70 and CD27 were expressed on CD68 + macrophages, CD27 was expressed on CAFs, and both molecules exhibited a partial coexpression with CD3. Furthermore, patients with high CD20 + B-cell densities or the presence of tertiary lymphoid structures (TLS) had significantly improved OS (p = 0.0017, HR: 0.491), suggesting the importance of B-cell-related immune responses in SCLC prognosis.</p><p><strong>Conclusion: </strong>CD70, B-cell density and the presence of TLSs, but not CD27, emerged as a significant prognostic biomarker for OS in surgically treated SCLC, suggesting its potential as a therapeutic target.</p>\",\"PeriodicalId\":9595,\"journal\":{\"name\":\"Cancer Immunology, Immunotherapy\",\"volume\":\"74 5\",\"pages\":\"165\"},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2025-04-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11981989/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Immunology, Immunotherapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00262-025-04006-2\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Immunology, Immunotherapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00262-025-04006-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer.
Introduction: Small cell lung cancer (SCLC) is a highly aggressive malignancy with poor survival outcomes. The CD70-CD27 axis has been implicated in immune regulation and tumor progression across cancers, but its role in SCLC has not yet been elucidated. This research explores the expression patterns and prognostic significance of CD70 and CD27 in early-stage SCLC.
Methods: In this retrospective study, we analyzed 190 surgically resected SCLC tumor samples using immunohistochemistry (IHC) for CD70 and CD27 expression and RNAscope for CD70 RNA detection. Immune infiltration was assessed using CD45, CD8, and CD20 staining. Quantification of RNAscope signals was performed using QPath software. Kaplan-Meier survival analysis and multivariate Cox regression were used to assess the prognostic impact of CD70, CD27, and immune cell infiltrates on overall survival (OS).
Results: CD70 was expressed in 46% of tumors, primarily within tumor nests, with lower expression in stromal areas. High CD70 expression correlated with significantly decreased OS (p = 0.0078, HR: 1.795) without any correlation with CD45 + , CD8 + or CD20 + immune cell infiltrates. CD27 expression was mainly confined to the stroma, and it did not show a significant association with OS (p = 0.582). Importantly, high CD27 expression was linked to reduced CD45 + and CD8 + cell densities in the stroma. Both CD70 and CD27 were expressed on CD68 + macrophages, CD27 was expressed on CAFs, and both molecules exhibited a partial coexpression with CD3. Furthermore, patients with high CD20 + B-cell densities or the presence of tertiary lymphoid structures (TLS) had significantly improved OS (p = 0.0017, HR: 0.491), suggesting the importance of B-cell-related immune responses in SCLC prognosis.
Conclusion: CD70, B-cell density and the presence of TLSs, but not CD27, emerged as a significant prognostic biomarker for OS in surgically treated SCLC, suggesting its potential as a therapeutic target.
期刊介绍：
Cancer Immunology, Immunotherapy has the basic aim of keeping readers informed of the latest research results in the fields of oncology and immunology. As knowledge expands, the scope of the journal has broadened to include more of the progress being made in the areas of biology concerned with biological response modifiers. This helps keep readers up to date on the latest advances in our understanding of tumor-host interactions.
The journal publishes short editorials including "position papers," general reviews, original articles, and short communications, providing a forum for the most current experimental and clinical advances in tumor immunology.
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