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Immune Cytolytic Activity Is Associated With Genetic and Clinical Properties of Glioma

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机构: [1]Department of Molecular Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China, [2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, [3]China National Clinical Research Center for Neurological Diseases, Beijing, China, [4]Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
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关键词: glioma immune cytolytic activity genetic clinical survival

摘要:
Background: Immunotherapy provided unprecedented advances in the treatment of several previously untreated cancers. However, these immunomodulatory maneuvers showed limited response to patients with glioma in clinical trials. Our aim was to depict the immune characteristics of glioma with immune cytolytic activity at genetic and transcriptome levels. Methods: In total, 325 gliomas from CGGA dataset as training cohort and 699 gliomas from TCGA dataset as validation cohort were enrolled in our analysis. We calculated the immune cytolytic activity for 1,000 of gliomas. The characteristics of immune cytolytic activity in gliomas were interpreted by the corresponding clinical, molecular genetics and radiological information. Results: We found that immune cytolytic activity was highly associated with molecular, clinical, and edema extent. High cytolytic activity gliomas were more likely to be diagnosed as glioblastoma and might be a potential marker of mesenchymal subtype. Moreover, those gliomas exhibited significantly increased copy number alterations including recurrent focal amplifications of PDGFA and EGFR, as well as recurrent deletions of CDKN2A/B. Subsequent biological function analysis revealed that the immune response and immune checkpoints expression were significantly correlated with the cytolytic activity of gliomas. Immune cytolytic activity was significantly positively associated with the extent of peri-tumor edema and was independently correlated with reduced survival time. Conclusion: Our results highlighted the immunoregulatory mechanism heterogeneity of gliomas. Cytolytic activity, indirectly reflected by the extent of peri-tumor edema, may provide a potential index to evaluate the status of immune microenvironment and immune checkpoints in glioma, which should be fully valued for precision classification and immunotherapy.

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出版当年[2018]版:
大类 | 2 区 医学
小类 | 2 区 免疫学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 免疫学
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出版当年[2017]版:
Q1 IMMUNOLOGY
最新[2023]版:
Q1 IMMUNOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2017版] 出版当年五年平均 出版前一年[2016版] 出版后一年[2018版]

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第一作者机构: [1]Department of Molecular Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China,
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通讯机构: [1]Department of Molecular Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China, [2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, [3]China National Clinical Research Center for Neurological Diseases, Beijing, China, [4]Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
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