Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer
Abstract 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...
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Springer
2025-04-01
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| Series: | Cancer Immunology, Immunotherapy |
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| Online Access: | https://doi.org/10.1007/s00262-025-04006-2 |
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| author | 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 |
| author_facet | 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 |
| author_sort | David Dora |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-b12e51cd368241df9690b83ca4f7a2ec |
| institution | DOAJ |
| issn | 1432-0851 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Springer |
| record_format | Article |
| series | Cancer Immunology, Immunotherapy |
| spelling | doaj-art-b12e51cd368241df9690b83ca4f7a2ec2025-08-20T03:13:57ZengSpringerCancer Immunology, Immunotherapy1432-08512025-04-0174511510.1007/s00262-025-04006-2Expression of costimulatory molecule CD70 is prognostic in small cell lung cancerDavid Dora0Zsolt Megyesfalvi1Imre Vörös2Ágnes Paál3Peter Takacs4Daniela Dobos5Bence Lőrincz6Syeda Mahak Zahra Bokhari7Kenan Aloss8Gergely Pallag9Christopher Rivard10Hui Yu11Fred R. Hirsch12Anikó Görbe13Zoltán V. Varga14Zoltan Lohinai15Balazs Dome16Department of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis UniversityDepartment of Tumor Biology, National Koranyi Institute of PulmonologyCardiometabolic and HUN-REN-SU System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis UniversityCardiometabolic and HUN-REN-SU System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis UniversityDepartment of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis UniversityDepartment of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis UniversityDepartment of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis UniversityTranslational Medicine Institute, Semmelweis UniversityTranslational Medicine Institute, Semmelweis UniversityDepartment of Anatomy, Histology, and Embryology, Faculty of Medicine, Semmelweis UniversityDivision of Medical Oncology, University of Colorado Anschutz Medical CampusDivision of Medical Oncology, University of Colorado Anschutz Medical CampusDivision of Medical Oncology, University of Colorado Anschutz Medical CampusCardiometabolic and HUN-REN-SU System Pharmacology Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis UniversityCenter for Pharmacology and Drug Research and Development, Semmelweis UniversityTranslational Medicine Institute, Semmelweis UniversityDepartment of Tumor Biology, National Koranyi Institute of PulmonologyAbstract 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.https://doi.org/10.1007/s00262-025-04006-2Small-cell lung cancerCD70CD27B-cellTLSTumor microenvironment |
| spellingShingle | 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 Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer Cancer Immunology, Immunotherapy Small-cell lung cancer CD70 CD27 B-cell TLS Tumor microenvironment |
| title | Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer |
| title_full | Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer |
| title_fullStr | Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer |
| title_full_unstemmed | Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer |
| title_short | Expression of costimulatory molecule CD70 is prognostic in small cell lung cancer |
| title_sort | expression of costimulatory molecule cd70 is prognostic in small cell lung cancer |
| topic | Small-cell lung cancer CD70 CD27 B-cell TLS Tumor microenvironment |
| url | https://doi.org/10.1007/s00262-025-04006-2 |
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