Interleukin-8-induced tumor self-rampart spatially confines oncolytic virotherapy in glioblastoma
文献类型：期刊论文
| 作者 | Jiang, Shan3,4; Xu, Houshi2,3,4; Sun, Maoyuan2,3,4; Xu, Yongfen10; Chai, Huihui2,3,4; Fan, Zhen2,3,4; Zhou, Zhirui1,2,3,4; Liu, Beining2,3,4; Wang, Yue2,3,4; Zhu, Ruize2,3,4 |
| 刊名 | NEURO-ONCOLOGY
 |
| 出版日期 | 2026-01-13 |
| 页码 | 16 |
| 关键词 | CRISPR screening glioblastoma interleukin-8 oncolytic adenovirus tumor self-rampart |
| ISSN号 | 1522-8517 |
| DOI | 10.1093/neuonc/noaf276 |
| 通讯作者 | Zhou, Liangfu(lfzhouc@126.com) ; Shi, Zhifeng(shizhifeng@fudan.edu.cn) |
| 英文摘要 | Background Oncolytic virotherapy holds promise for Glioblastoma (GBM), but the intratumoral replication kinetics of oncolytic viruses and resistance mechanisms of tumor cells remain poorly understood, limiting the development of precise combination strategies to improve durable efficacy.Methods Using the translational Resistance Exploration via Synchronized Clinical-Unit Experiments (RESCUE) framework that synchronizes clinical trials with patient-derived xenograft (PDX) models, we profiled the replication kinetics of the oncolytic adenovirus YSCH-01 and performed genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) activation screening to identify key genes restricting sustained viral replication. Through spatial transcriptomics combined with histological analyses, we delineated the spatial determinants that limit viral dissemination following oncolytic virus administration.Results We identified B-cell lymphoma/leukemia 10 (BCL10) as a key suppressor of sustained viral replication. Viral infection activated the BCL10-NF-kappa B pathway, triggering paracrine secretion of interleukin-8 (IL-8) from infected tumor cells. Interleukin-8 induced senescence and fibrotic remodeling in neighboring uninfected cells, forming a previously unrecognized Tumor Self-Rampart (TSR)-a concentric barrier of senescent and fibrotic tumor cells that spatially confines viral propagation. Tumor Self-Rampart was validated in both PDX and patient tumors. Interleukin-8 blockade with Reparixin or peri-dosing glucocorticoids effectively disrupted TSR formation, prolonged viral persistence, and enhanced therapeutic efficacy.Conclusion Glioblastoma mounts a spatial self-protective defense through IL-8-driven TSR formation that restricts oncolytic virus spread. Interleukin-8 functions as both a pharmacodynamic biomarker and a therapeutic target, and its inhibition provides a rational strategy to overcome resistance and optimize GBM virotherapy. |
| WOS关键词 | RECURRENT GBM ; ADENOVIRUS ; TRIAL ; NEUTROPHILS ; DELIVERY ; PHASE-1 ; VIRUS ; SERUM |
| 资助项目 | National Key R&D Program of China[2023YFC2510003, 2023YFC2510000, 2024YFA1210201, 2022YFF1202804] ; Excellent project of Shanghai Municipal Health Commission[20234Z0009] ; Shanghai Municipal Education Commission ; Shanghai Science and Technology Commission, Dawn Program of Shanghai Education Commission[23SG07] ; Ministry of Science and Technology of the People's Republic of China (PRC), National Natural Science Foundation of China[82373018, 82473295] ; Shanghai Municipal Health Commission, Medical innovation research project of Shanghai Science and Technology Commission[23Y11906200] |
| WOS研究方向 | Oncology ; Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:001660341600001 |
| 出版者 | OXFORD UNIV PRESS INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322581]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Zhou, Liangfu; Shi, Zhifeng |
| 作者单位 | 1.Fudan Univ, Huashan Hosp, Shanghai Med Coll, Radiat Oncol Ctr, Shanghai, Peoples R China 2.Fudan Univ, Neurosurg Inst, Shanghai, Peoples R China 3.Natl Ctr Neurol Disorders, Shanghai, Peoples R China 4.Fudan Univ, Huashan Hosp, Dept Neurosurg, 958 Jingguang Rd, Shanghai 200040, Peoples R China 5.Jinfeng Lab, Chongqing, Peoples R China 6.Army Med Univ, Southwest Hosp, Southwest Canc Ctr, Chongqing, Peoples R China 7.Army Med Univ, Southwest Hosp, Inst Pathol, Chongqing, Peoples R China 8.Fujian Med Univ, Affiliated Hosp 1, Dept Neurosurg, Fuzhou, Fujian, Peoples R China 9.Zhejiang Sci Tech Univ, Inst Smart Biomed Mat, Hangzhou, Peoples R China 10.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Jiang, Shan,Xu, Houshi,Sun, Maoyuan,et al. Interleukin-8-induced tumor self-rampart spatially confines oncolytic virotherapy in glioblastoma[J]. NEURO-ONCOLOGY,2026:16. |
| APA | Jiang, Shan.,Xu, Houshi.,Sun, Maoyuan.,Xu, Yongfen.,Chai, Huihui.,...&Shi, Zhifeng.(2026).Interleukin-8-induced tumor self-rampart spatially confines oncolytic virotherapy in glioblastoma.NEURO-ONCOLOGY,16. |
| MLA | Jiang, Shan,et al."Interleukin-8-induced tumor self-rampart spatially confines oncolytic virotherapy in glioblastoma".NEURO-ONCOLOGY (2026):16. |
入库方式： OAI收割
来源：上海药物研究所
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