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Transcriptomics-based characterization of the immuno-stromal microenvironment in pediatric low-grade glioma.
Körner, Meik; Spohn, Michael; Schüller, Ulrich; Bockmayr, Michael.
Affiliation
  • Körner M; Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
  • Spohn M; Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.
  • Schüller U; Research Institute Children's Cancer Center Hamburg, Hamburg, Germany.
  • Bockmayr M; Bioinformatics Core, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Oncoimmunology ; 13(1): 2386789, 2024.
Article in En | MEDLINE | ID: mdl-39135890
ABSTRACT
Immunologic treatment options are uncommon in low-grade gliomas, although such therapies might be beneficial for inoperable and aggressive cases. Knowledge of the immune and stromal cells in low-grade gliomas is highly relevant for such approaches but still needs to be improved. Published gene-expression data from 400 low-grade gliomas and 193 high-grade gliomas were gathered to quantify 10 microenvironment cell populations with a deconvolution method designed explicitly for brain tumors. First, we investigated general differences in the microenvironment of low- and high-grade gliomas. Lower-grade and high-grade tumors cluster together, respectively, and show a general similarity within and distinct differences between these groups, the main difference being a higher infiltration of fibroblasts and T cells in high-grade gliomas. Among the analyzed entities, gangliogliomas and pleomorphic xanthoastrocytomas presented the highest overall immune cell infiltration. Further analyses of the low-grade gliomas presented three distinct microenvironmental signatures of immune cell infiltration, which can be divided into T-cell/dendritic/natural killer cell-, neutrophilic/B lineage/natural killer cell-, and monocytic/vascular/stromal-cell-dominated immune clusters. These clusters correlated with tumor location, age, and histological diagnosis but not with sex or progression-free survival. A survival analysis showed that the prognosis can be predicted from gene expression, clinical data, and a combination of both with a support vector machine and revealed the negative prognostic relevance of vascular markers. Overall, our work shows that low- and high-grade gliomas can be characterized and differentiated by their immune cell infiltration. Low-grade gliomas cluster into three distinct immunologic tumor microenvironments, which may be of further interest for upcoming immunotherapeutic research.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / Tumor Microenvironment / Glioma Limits: Adolescent / Child / Child, preschool / Female / Humans / Male Language: En Journal: Oncoimmunology Year: 2024 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / Tumor Microenvironment / Glioma Limits: Adolescent / Child / Child, preschool / Female / Humans / Male Language: En Journal: Oncoimmunology Year: 2024 Document type: Article