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Updated: Dec 8, 2025
Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Bip inhibition in glioma stem cells promotes radiation-induced immunogenic cell death
Wei Yang1, Zenghe Xiu2, Yuping He2
1State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection and Collaborative InnovationCenter of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu, China. detachedy@aliyun.com.
Abstract:
Tumor regression in sites distant to the irradiated field are thought to be associated with emission of damage-associated molecular patterns (DAMPs) molecules and generation of immunogenic cell death (ICD). Glioma stem cells (GSCs) are resistant to high doses of radiation, and ultimately select the outgrowth of a more aggressive tumor. This study showed high-dose IR triggered fewer DAMPs molecules exposure and release in GSCs comparing to matched non-GSCs. Downregulation of binding immunoglobulin protein (Bip) promoted IR-mediated endoplasmic reticulum stress to generate DAMPs molecules by PERK and IRE1-α phosphorylation, and increased dendritic cells mature and effector T lymphocytes activation. GSCs treated with Bip knockdown and IR efficiently prevented tumor generation, and reduced post-radiotherapy tumor recurrence. These data suggest that Bip plays a critical role in inhibition of IR-induced ICD in GSCs, and Bip inhibition may be a promising strategy on adjuvant therapy by ameliorating tumor immune microenvironment.
Insights
High-dose radiation triggers fewer damage-associated molecular patterns (DAMPs) in glioma stem cells (GSCs). Inhibiting binding immunoglobulin protein (Bip) enhances radiation-induced immunogenic cell death (ICD) in GSCs, reducing tumor recurrence.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Tumor regression at distant sites is linked to damage-associated molecular patterns (DAMPs) and immunogenic cell death (ICD).
- Glioma stem cells (GSCs) exhibit resistance to radiation, leading to aggressive tumor recurrence.
- Radiation therapy (IR) effectiveness is limited by GSC radioresistance and insufficient immune response.
Purpose of the Study:
- To investigate the role of binding immunoglobulin protein (Bip) in radiation-induced immunogenic cell death (ICD) in GSCs.
- To explore Bip inhibition as a potential adjuvant therapy to enhance anti-tumor immunity in gliomas.
Main Methods:
- Comparison of DAMPs release in GSCs versus non-GSCs after high-dose IR.
- Assessment of endoplasmic reticulum (ER) stress pathways (PERK, IRE1-α) following Bip knockdown.
- Evaluation of dendritic cell maturation and T lymphocyte activation.
- In vivo studies assessing tumor generation and recurrence after Bip knockdown and IR treatment.
Main Results:
- High-dose IR induced significantly lower DAMPs exposure and release in GSCs compared to non-GSCs.
- Downregulation of Bip promoted IR-mediated ER stress via PERK and IRE1-α phosphorylation.
- Bip knockdown combined with IR enhanced dendritic cell maturation and effector T lymphocyte activation.
- Combined Bip inhibition and IR treatment prevented tumor formation and reduced recurrence in vivo.
Conclusions:
- Bip plays a crucial role in suppressing IR-induced ICD in GSCs.
- Inhibiting Bip enhances the immunogenic potential of radiation therapy in gliomas.
- Bip inhibition represents a promising adjuvant therapeutic strategy to improve the tumor immune microenvironment and combat GSC radioresistance.
