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Updated: Oct 25, 2025

Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
CYB561D2 up-regulation activates STAT3 to induce immunosuppression and aggression in gliomas
Bangbao Tao1, Juanhong Shi2, Shuai Shuai3
1Department of Neurosurgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, 1665 Kongjiang Road, Shanghai, 200092, China.
Background:
Fine tuned balance of reactive oxygen species (ROS) is essential for tumor cells and tumor cells use immune checkpoints to evade attack form immunity system. However, it's unclear whether there is any crosstalk between these two pathways. CYB561D2, an antioxidant protein, is part of 5-gene prognosis signature in gliomas and its involvement in gliomas is unknown. Here, we aim to provide a detailed characterization of CYB561D2 in gliomas.
Methods:
CYB561D2 expression was measured in clinical samples of gilomas and normal tissues. The effects of CYB561D2 on immunity related genes and tumor behaviors were investigated in glioma cell lines with various in vitro and in vivo assays.
Results:
CYB561D2 expression was enhanced in gliomas compared to control tissues. CYB561D2 up-regulation was associated with high grading of gliomas and short survival in patients. CYB561D2 expression was induced by H2O2 in glioma cell lines. CYB561D2 and its functional product ascorbate activated STAT3 dose-dependently. CYB561D2 over-expression increased PD-L1, CCL2 and TDO2 expression, and induced immunosuppression in co-cultured T cells. In in vitro assays, CYB561D2 knock-down suppressed cell growth, colony formation, migration and promoted apoptosis. In contrast, CYB561D2 over-expression reduced survival rate in intracranial glioma model and this effect could be blocked by dominant negative-STAT3. The CYB561D2 up-regulation and the positive association of CYB561D2 with PD-L1, CCL2 and TDO2 expression were cross-validated in open-access datasets.
Conclusions:
CYB561D2 up-regulation induces immunosuppression and aggression via activating STAT3 in gliomas and CYB561D2 mediates ROS-tumor immunity crosstalk.
Insights
This study reveals that CYB561D2 protein promotes glioma progression by activating STAT3, leading to immune suppression. Understanding this reactive oxygen species-tumor immunity crosstalk is key for glioma treatment.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Reactive oxygen species (ROS) balance is crucial for tumor cells.
- Tumor cells utilize immune checkpoints to evade immune responses.
- The interplay between ROS and immune checkpoints in gliomas is not well understood.
Purpose of the Study:
- To investigate the role of CYB561D2, an antioxidant protein and glioma prognostic marker, in gliomas.
- To elucidate the mechanisms by which CYB561D2 influences glioma progression and immune evasion.
Main Methods:
- CYB561D2 expression analysis in clinical glioma samples and normal tissues.
- In vitro and in vivo assays in glioma cell lines to assess CYB561D2 effects on tumor behavior and immunity.
- Validation using open-access datasets.
Main Results:
- CYB561D2 expression is elevated in gliomas, correlating with higher grade and poorer survival.
- CYB561D2 activates STAT3, upregulating immunosuppressive genes (PD-L1, CCL2, TDO2) and promoting glioma cell growth, migration, and apoptosis resistance.
- CYB561D2 overexpression reduces survival in vivo, an effect mitigated by STAT3 inhibition.
Conclusions:
- CYB561D2 upregulation drives glioma aggression and immunosuppression through STAT3 activation.
- CYB561D2 acts as a mediator in the crosstalk between reactive oxygen species and tumor immunity in gliomas.
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