Bip inhibition in glioma stem cells promotes radiation-induced immunogenic cell death
Wei Yang, Zenghe Xiu, Yu‐Ping He, Wenpeng Huang, Yanyan Li, Ting Sun
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.