Article
Gene expression profile of glioblastoma cells from patients with long-term survival treated with dendritic cell immunotherapy
Gen-Expressionsprofil von Glioblastomzellen von langzeitüberlebenden, Patienten, die mit einer dendritischen Zell-Immuntherapie behandelt wurden
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Authors
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Jun Takei
- The Jikei University School of Medicine, Division of Oncology, Research Centre for Medical Sciences, Tokio, Japan; The Jikei University School of Medicine, Department of Neurosurgery, Tokio, Japan
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Yuko Kamata
- The Jikei University School of Medicine, Division of Oncology, Research Centre for Medical Sciences, Tokio, Japan
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Yasuharu Akasaki
- The Jikei University School of Medicine, Department of Neurosurgery, Tokio, Japan
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Ryosuke Mori
- The Jikei University School of Medicine, Department of Neurosurgery, Tokio, Japan
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Yohei Yamamoto
- Jikei University Daisan Hospital, Department of Neurosurgery, Tokio, Japan
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Toshihide Tanaka
- Jikei University Kashiwa Hospital, Department of Neurosurgery, Chiba, Japan
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Mutsunori Murahashi
- The Jikei University School of Medicine, Division of Oncology, Research Centre for Medical Sciences, Tokio, Japan
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Yuichi Murayama
- The Jikei University School of Medicine, Department of Neurosurgery, Tokio, Japan
| Published: | June 26, 2020 |
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Outline
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Objective: Glioblastoma is the most malignant brain tumour of the central nervous system tumours. Dendritic cells (DCs) perform an essential role in the immune system as antigen-presenting cells. Immunotherapy with DCs for glioblastoma is expected to improve the therapeutic outcome for patients by inducing tumour-specific cytotoxic T cells. Previously we reported the effectiveness of immunotherapy with fusion cells (FCs) obtained by merging DCs and patient-derived tumour cells in a phase I/II clinical trial. In this trial, median overall survival reached 30 months for the patients with newly diagnosed glioblastoma. The main aim of this study was to investigate the differences in gene expression and tumour characteristics between patients with long and short survival times.
Methods: We collected patient-derived tumour samples from adults with a newly diagnosed glioblastoma who underwent immunotherapy with FCs from 2006 to 2014. Total RNA was extracted from patient-derived tumour cells using RNeasy plus kit (QIAGEN). mRNA was extracted using Dynabeads mRNA DIRECT Micro kit (Thermo Fisher) and the library was prepared using Ion Total RNASeq kit v2 (Thermo Fisher). Ion chef (Thermo Fisher) and Ion Proton (Thermo Fisher) were used to perform next generation sequencing for whole transcriptome analysis. The samples were divided into two groups in accordance with the patient's overall survival, long-term survivors’ samples (group L, 3 years or more survival period) and short-term survivors’ samples (group S, less than 3 years survival period). Differential expression analysis between the two groups was carried out using CLC Genomics Workbench (QIAGEN). Genes with fold change > 2 were identified as differentially expressed genes. Gene Ontologies (GO) were assigned and enrichment analysis was carried out using CLC Genomics Workbench.
Results: Whole transcriptome analysis was performed for 6 samples, out of which 2 belonged to group L and 4 belonged to group S. GO enrichment analysis revealed that GO terms for "anatomical structure formation involved in morphogenesis" and "cell differentiation" were over-represented in Group L and Group S, respectively. The GO terms of group L had 7 differentially expressed genes, while the group S had 27 differentially expressed genes.
Conclusion: Patients treated with FCs immunotherapy using patient-derived glioblastoma cells which had high expression of cell differentiation-related genes might tend to have a poor prognosis.
