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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.01756

Immune cytolytic activity is associated with genetic and clinical properties of glioma

 Tao Jiang1*, Zhiliang Wang1, Zheng Wang1, Guanzhang Li1, Qiangwei Wang1, Zhaoshi Bao1 and ChuanBao Zhang1
  • 1Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, China

Abstract
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 thousands 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.

Keywords: Glioma, immune cytolytic activity, genetic, clinical, Survival

Received: 16 Aug 2018; Accepted: 11 Jul 2019.

Edited by:

Katy Rezvani, University of Texas MD Anderson Cancer Center, United States

Reviewed by:

Arya Biragyn, National Institute on Aging (NIA), United States
Carlos Alfaro, NavarraBiomed, Spain  

Copyright: © 2019 Jiang, Wang, Wang, Li, Wang, Bao and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Tao Jiang, Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, Beijing, China, taojiang1964@163.com