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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Main Authors: Jianan Chen, Qiong Wu, Anders E. Berglund, Robert J. Macaulay, Arnold B. Etame
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/2/66
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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
collection DOAJ
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.
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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
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AT qiongwu comprehensiveanalysisidentifiesithemis2iasapotentialprognosticandimmunologicalbiomarkeringlioblastoma
AT anderseberglund comprehensiveanalysisidentifiesithemis2iasapotentialprognosticandimmunologicalbiomarkeringlioblastoma
AT robertjmacaulay comprehensiveanalysisidentifiesithemis2iasapotentialprognosticandimmunologicalbiomarkeringlioblastoma
AT arnoldbetame comprehensiveanalysisidentifiesithemis2iasapotentialprognosticandimmunologicalbiomarkeringlioblastoma