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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Bibliographic Details
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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Summary: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.
ISSN:2073-4409