Comprehensive Analysis Identifies <i>THEMIS2</i> as a Potential Prognostic and Immunological Biomarker in Glioblastoma
Glioblastoma (GBM) is a highly aggressive brain tumor characterized by its ability to evade the immune system, hindering the efficacy of current immunotherapies. Recent research has highlighted the important role of immunosuppressive macrophages in the tumor microenvironment (TME) in driving this im...
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2025-01-01
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author | Jianan Chen Qiong Wu Anders E. Berglund Robert J. Macaulay Arnold B. Etame |
author_facet | Jianan Chen Qiong Wu Anders E. Berglund Robert J. Macaulay Arnold B. Etame |
author_sort | Jianan Chen |
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description | Glioblastoma (GBM) is a highly aggressive brain tumor characterized by its ability to evade the immune system, hindering the efficacy of current immunotherapies. Recent research has highlighted the important role of immunosuppressive macrophages in the tumor microenvironment (TME) in driving this immune evasion. In this study, we are the first to identify <i>THEMIS2</i> as a key regulator of tumor-associated macrophage (TAM)-mediated immunosuppression in GBM. We found that a high <i>THEMIS2</i> expression is associated with poor patient outcomes and increased infiltration of immune cells, particularly macrophages. Functional analyses revealed <i>THEMIS2</i>’s critical involvement in immune-related pathways, including immune response activation, mononuclear cell differentiation, and the positive regulation of cytokine production. Additionally, single-cell RNA sequencing data demonstrated that macrophages with a high <i>THEMIS2</i> expression were associated with increased phagocytosis, immune suppression, and enhanced tumor growth. These findings suggest that <i>THEMIS2</i> could serve as both a prognostic marker and a therapeutic target for enhancing anti-tumor immunity in GBM. |
format | Article |
id | doaj-art-7d0194bcc99a455cbe081cbbdf8b18c8 |
institution | Kabale University |
issn | 2073-4409 |
language | English |
publishDate | 2025-01-01 |
publisher | MDPI AG |
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series | Cells |
spelling | doaj-art-7d0194bcc99a455cbe081cbbdf8b18c82025-01-24T13:26:33ZengMDPI AGCells2073-44092025-01-011426610.3390/cells14020066Comprehensive Analysis Identifies <i>THEMIS2</i> as a Potential Prognostic and Immunological Biomarker in GlioblastomaJianan Chen0Qiong Wu1Anders E. Berglund2Robert J. Macaulay3Arnold B. Etame4Department of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USADepartment of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USADepartment of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USADepartments of Anatomic Pathology, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USADepartment of Neuro-Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USAGlioblastoma (GBM) is a highly aggressive brain tumor characterized by its ability to evade the immune system, hindering the efficacy of current immunotherapies. Recent research has highlighted the important role of immunosuppressive macrophages in the tumor microenvironment (TME) in driving this immune evasion. In this study, we are the first to identify <i>THEMIS2</i> as a key regulator of tumor-associated macrophage (TAM)-mediated immunosuppression in GBM. We found that a high <i>THEMIS2</i> expression is associated with poor patient outcomes and increased infiltration of immune cells, particularly macrophages. Functional analyses revealed <i>THEMIS2</i>’s critical involvement in immune-related pathways, including immune response activation, mononuclear cell differentiation, and the positive regulation of cytokine production. Additionally, single-cell RNA sequencing data demonstrated that macrophages with a high <i>THEMIS2</i> expression were associated with increased phagocytosis, immune suppression, and enhanced tumor growth. These findings suggest that <i>THEMIS2</i> could serve as both a prognostic marker and a therapeutic target for enhancing anti-tumor immunity in GBM.https://www.mdpi.com/2073-4409/14/2/66macrophage-mediated immunosuppressionglioblastoma<i>THEMIS2</i>tumor microenvironmentprognosis |
spellingShingle | Jianan Chen Qiong Wu Anders E. Berglund Robert J. Macaulay Arnold B. Etame Comprehensive Analysis Identifies <i>THEMIS2</i> as a Potential Prognostic and Immunological Biomarker in Glioblastoma Cells macrophage-mediated immunosuppression glioblastoma <i>THEMIS2</i> tumor microenvironment prognosis |
title | Comprehensive Analysis Identifies <i>THEMIS2</i> as a Potential Prognostic and Immunological Biomarker in Glioblastoma |
title_full | Comprehensive Analysis Identifies <i>THEMIS2</i> as a Potential Prognostic and Immunological Biomarker in Glioblastoma |
title_fullStr | Comprehensive Analysis Identifies <i>THEMIS2</i> as a Potential Prognostic and Immunological Biomarker in Glioblastoma |
title_full_unstemmed | Comprehensive Analysis Identifies <i>THEMIS2</i> as a Potential Prognostic and Immunological Biomarker in Glioblastoma |
title_short | Comprehensive Analysis Identifies <i>THEMIS2</i> as a Potential Prognostic and Immunological Biomarker in Glioblastoma |
title_sort | comprehensive analysis identifies i themis2 i as a potential prognostic and immunological biomarker in glioblastoma |
topic | macrophage-mediated immunosuppression glioblastoma <i>THEMIS2</i> tumor microenvironment prognosis |
url | https://www.mdpi.com/2073-4409/14/2/66 |
work_keys_str_mv | AT jiananchen comprehensiveanalysisidentifiesithemis2iasapotentialprognosticandimmunologicalbiomarkeringlioblastoma AT qiongwu comprehensiveanalysisidentifiesithemis2iasapotentialprognosticandimmunologicalbiomarkeringlioblastoma AT anderseberglund comprehensiveanalysisidentifiesithemis2iasapotentialprognosticandimmunologicalbiomarkeringlioblastoma AT robertjmacaulay comprehensiveanalysisidentifiesithemis2iasapotentialprognosticandimmunologicalbiomarkeringlioblastoma AT arnoldbetame comprehensiveanalysisidentifiesithemis2iasapotentialprognosticandimmunologicalbiomarkeringlioblastoma |