The Spatiotemporal Evolution of Radiation Resistance in Glioblastoma
BACKGROUND: 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. METHODS: The radio-resistance signature score (RRSS) was calculated by utilizing glioma sphere-forming cells (GSCs) which recapitulate the transcriptomic landscape of GBM. RESULTS: 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. CONCLUSIONS: Our study revealed the spatiotemporal evolution of radiation resistance of GBM, and shed light on the development of novel adjuvant therapeutic strategies.
Authors
- Qianghu Wang (ORCID: https://orcid.org/0000-0002-3488-1059)
- Ravesanker Ezhilarasan (ORCID: https://orcid.org/0000-0002-1353-8307)
- Apeng Chen (ORCID: https://orcid.org/0000-0002-1936-2007)
- Erik P. Sulman (ORCID: https://orcid.org/0000-0003-4933-9120)
- Fengqi Zhou (ORCID: https://orcid.org/0009-0006-9320-4062)
- Yingwen Ding (ORCID: https://orcid.org/0000-0001-7673-8499)
- Jiankai Yang
- Joy Gumin
- Lindsey D. Goodman (ORCID: https://orcid.org/0000-0002-9255-3811)
- Mengyan Zhu (ORCID: https://orcid.org/0000-0003-2953-8309)
- Xu Qian
- Ze-Yan Zhang (ORCID: https://orcid.org/0000-0002-7896-3013)
- Roel G W Verhaak
- Peng Xia
- Benqing Yu
- Guojing Wu
- Ananya Jambhale
- Runheng Huang
- Yu Shi
- Ning Wang
- Zhangchun Cheng
- W K Alfred Yung
- Yongping You
- Fan Lin
- Miao Yu
- Baoli Hu
- Junxia Zhang
- Min Wu
- Xiuxing Wang
- Lei Cheng
- Bin Huang
- Wei Wu
- Lingxiang Wu
- Krishna Bhat
- Quanzhong Liu
- Jian Chen
- Frederick F Lang
- Kenneth D Aldape
- Zheng Zhao
Institutions
- Hebei Medical University (CN)
- The University of Texas MD Anderson Cancer Center (US)
- Army Medical University (CN)
- University of Pittsburgh (US)
- Duke University (US)
- Capital Medical University (CN)
- Yale University (US)
- NYU Langone Health (US)
- Beijing Tian Tan Hospital (CN)
- Cal Humanities (US)
- Nanjing Children's Hospital (CN)
- Southeast University (BD)
- Shanghai Children's Medical Center (CN)
- Huaian First People’s Hospital (CN)
- Second Hospital of Hebei Medical University (CN)
- Nanjing Drum Tower Hospital (CN)
- Beijing Institute of Neurosurgery (CN)
- Chinese Institute for Brain Research (CN)
- Neurological Research Institute (US)
- Mayo Clinic in Arizona (US)
- Mayo Clinic Hospital (US)
- Jiangsu Cancer Hospital (CN)
- Children's Hospital of Pittsburgh (US)
- Southwest Hospital (CN)
- Second Affiliated Hospital of Nanjing Medical University (CN)
- National Cancer Institute (US)
- Duke University Health System (US)
- Tumor Hospital of Guangxi Medical University (CN)
- Pediatric Brain Tumor Foundation (US)
- New York University (US)
- Southeast University (CN)
- Nanjing Medical University (CN)
Publication Details
- Journal
- Neuro-Oncology
- Published
- 2026-09-14
- DOI
- https://doi.org/10.1093/neuonc/noag209
- Primary Topic
- Glioma Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00