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Gemistocytic tumor cells programmed for glial scarring characterize T cell confinement in IDH-mutant astrocytoma.
Nat Commun
January 2025
Department of Medical Oncology, Laboratory of Tumor Immunology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Isocitrate dehydrogenase 1/2 mutant (IDHmt) astrocytoma is considered a T cell-deprived tumor, yet little is known regarding the phenotypes underlying T cell exclusion. Using bulk, single nucleus and spatial RNA and protein profiling, we demonstrate that a distinct spatial organization underlies T cell confinement to the perivascular space (T cell cuff) in IDHmt astrocytoma. T cell cuffs are uniquely characterized by a high abundance of gemistocytic tumor cells (GTC) in the surrounding stroma.
View Article and Find Full Text PDFInferring the genetic relationships between unsupervised deep learning-derived imaging phenotypes and glioblastoma through multi-omics approaches.
Brief Bioinform
November 2024
Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
This study aimed to investigate the genetic association between glioblastoma (GBM) and unsupervised deep learning-derived imaging phenotypes (UDIPs). We employed a combination of genome-wide association study (GWAS) data, single-nucleus RNA sequencing (snRNA-seq), and scPagwas (pathway-based polygenic regression framework) methods to explore the genetic links between UDIPs and GBM. Two-sample Mendelian randomization analyses were conducted to identify causal relationships between UDIPs and GBM.
View Article and Find Full Text PDFTetraspanins 10 and 15 support Venezuelan equine encephalitis virus replication in astrocytoma cells.
Mol Biol Cell
January 2025
Institute for Biochemistry & Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Hannover, Germany.
Tetraspanins (Tspans) are transmembrane proteins that coordinate life cycle steps of viruses from distinct families. Here, we identify the human Tspan10 and Tspan15, both members of the TspanC8 subfamily, as replication factors for alphavirus Venezuelan equine encephalitis virus (VEEV) in astrocytoma cells. Pharmacological inhibition and siRNA-mediated silencing of TspanC8 interactor a disintegrin and metalloproteinase 10 (ADAM10) reduced VEEV infection.
View Article and Find Full Text PDFTargeting glycolysis: exploring a new frontier in glioblastoma therapy.
Front Immunol
January 2025
Department of Oncology, Suining Central Hospital, Suining, Sichuan, China.
Glioblastoma(GBM) is a highly malignant primary central nervous system tumor that poses a significant threat to patient survival due to its treatment resistance and rapid recurrence.Current treatment options, including maximal safe surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy, have limited efficacy.In recent years, the role of glycolytic metabolic reprogramming in GBM has garnered increasing attention.
View Article and Find Full Text PDFSodium valproate enhances efficacy of NKG2D CAR-T cells against glioblastoma.
Front Immunol
January 2025
Guangdong Immune Cell Therapy Engineering and Technology Research Center, Center for Protein and Cell-based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Chimeric antigen receptor T-cell (CAR-T) therapies have shown promise in glioblastoma clinical studies, but responses remain inconsistent due to heterogeneous tumor antigen expression and immune evasion post-treatment. NKG2D CAR-T cells have demonstrated a favorable safety profile in patients with hematologic tumors, and showed robust antitumor efficacy in various xenograft models, including glioblastoma. However, malignant glioma cells evade immunological surveillance by reducing NKG2D ligands expression or cleavage.
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