Metadata language
Kamińska-Kaczmarek, Bożena (1961– ) : Supervisor
Publisher:Nencki Institute of Experimental Biology PAS
Place of publishing: Date issued/created: Description:93 pages : illustrations ; 30 cm ; Bibliography ; Summary in Polish
Degree name: Degree discipline : Degree grantor:Nencki Institute of Experimental Biology PAS ; degree obtained 10.10.2025
Type of object: Subject and Keywords:Glioma ; Immunology ; scRNA-seq
Abstract:
The tumor microenvironment (TME) plays a critical role in glioblastoma (GBM) progression and therapy resistance. The immune composition of the TME and the interactions among immune cells in genetically engineered glioma models remain poorly characterized. Using single-cell RNA sequencing (scRNA- seq) with a panel of antibodies (CITE-seq) and Visium Spatial Transcriptomics, I performed a comprehensive analysis of the immune cell composition in GL261 gliomas, focusing on functional phenotypes of myeloid cells, T cells, and NK cells, in order to create the best to date description of TME in the most popular high- grade glioma (HGG) model. Building on prior work, I redefined macrophages into four functionally distinct states, demonstrating that higher cluster counts in earlier studies arise from over-clustering and reduce translational relevance, while expanding phenotypic characterization to include metabolic and spatial dynamics. In the lymphoid compartment, I identified all major T cell populations and determined their distribution and ratios, consistent with the GL261 glioma moderate immunogenicity. NK cells exhibited a glioma-associated phenotype with reduced cytotoxicity and increased expression of tumor-promoting factors. Ligand-receptor analyses highlighted the immunosuppressive interactions between macrophages and lymphoid cells, further emphasizing the role of myeloid cells in T cell suppression. To study the effects of the IDH1 R132H mutation on the immune TME, I employed CITE-seq and Spatial Transcriptomics in genetically defined mouse models. 2-hydroxyglutarate (2-HG), metabolite produced by cells with IDH1 mutation, suppressed T cell proliferation, metabolic activity, and oxidative phosphorylation while impairing myeloid antigen presentation and T cell recruitment. These findings underscore the complex interplay between glioma- associated factors and the immune microenvironment, offering new insights into tumor progression and potential therapeutic targets. This study advances our understanding of glioma TME heterogeneity, particularly in GL261 and IDH1-mutant HGG models, providing a robust framework for translational research and therapeutic development.
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Copyright holder:Publication made available with the written permission of the author
Digitizing institution:Nencki Institute of Experimental Biology of the Polish Academy of Sciences
Original in:Library of the Nencki Institute of Experimental Biology PAS
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