机构:[1]Department of Molecular Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China,研究所北京市神经外科研究所首都医科大学附属天坛医院[2]Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China,重点科室诊疗科室神经外科神经外科首都医科大学附属天坛医院[3]China National Clinical Research Center for Neurological Diseases, Beijing, China,[4]Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
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.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81761168038, 81802483, 81672479, 81702460]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special [ZYLX201708]; Beijing Nova ProgramBeijing Municipal Science & Technology Commission [Z171100001117022]
第一作者机构:[1]Department of Molecular Pathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China,
通讯作者:
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
推荐引用方式(GB/T 7714):
Zhi-liang Wang,Zheng Wang,Guan-zhang Li,et al.Immune Cytolytic Activity Is Associated With Genetic and Clinical Properties of Glioma[J].FRONTIERS IN IMMUNOLOGY.2019,10:-.doi:10.3389/fimmu.2019.01756.
APA:
Zhi-liang Wang,Zheng Wang,Guan-zhang Li,Qiang-wei Wang,Zhao-shi Bao...&Tao Jiang.(2019).Immune Cytolytic Activity Is Associated With Genetic and Clinical Properties of Glioma.FRONTIERS IN IMMUNOLOGY,10,
MLA:
Zhi-liang Wang,et al."Immune Cytolytic Activity Is Associated With Genetic and Clinical Properties of Glioma".FRONTIERS IN IMMUNOLOGY 10.(2019):-