The Spatiotemporal Evolution of Radiation Resistance in Glioblastoma.

Authors

Lingxiang Wu, Lei Cheng, Bin Huang, Runheng Huang, Ravesanker Ezhilarasan, Junxia Zhang, Wei Wu, Guojing Wu, Benqing Yu, Lindsey D Goodman, Ananya Jambhale, Baoli Hu, Apeng Chen, Mengyan Zhu, Min Wu, Peng Xia, Quanzhong Liu, Miao Yu, Zheng Zhao, Zhangchun Cheng, Ning Wang, Fan Lin, Fengqi Zhou, Ze-Yan Zhang, Yingwen Ding, Jian Chen, Xu Qian, Xiuxing Wang, Yu Shi, Joy Gumin, Krishna Bhat, W K Alfred Yung, Kenneth D Aldape, Roel G W Verhaak, Frederick F Lang, Yongping You, Jiankai Yang, Qianghu Wang, Erik P Sulman

Published in

Neuro-oncology. Sep 15, 2026. Epub Sep 15, 2026.

Abstract

Although radiation therapy (RT) remains one of the most effective treatments for patients with the lethal brain tumor glioblastoma (GBM), quite a number of patients show resistance or relapse shortly after RT. There is an urgent need to uncover the temporal and spatial dynamics of RT resistance during tumor progression and treatment.
The radio-resistance signature score (RRSS) was calculated by utilizing glioma sphere-forming cells (GSCs) which recapitulate the transcriptomic landscape of GBM.
RRSS can assess the RT response on both cell lines and GBM patients. Both transdifferentiated and irradiated glioma cells show increased radiation resistance, demonstrating that the recurrent GBM may acquire resistance along with cell differentiation and selective advantage during treatment. Moreover, RRSS of the marginal tumors is found to be higher than that of core tumors (Wilcoxon's rank-sum test, p-value<0.01). The infiltration of macrophages was significantly associated with radiation resistance (p-value<0.01), which was further validated by single-cell RNAseq based experiments and clonogenic assays. Moreover, we demonstrated that IL1B, a pro-inflammatory cytokine secreted by macrophages, could enhance the radiation resistance of tumor cells.
Our study revealed the spatiotemporal evolution of radiation resistance of GBM, and shed light on the development of novel adjuvant therapeutic strategies.

PMID:
42742387
Bibliographic data and abstract were imported from PubMed on 15 Sep 2026.

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