Overcoming therapeutic resistance in oncolytic herpes virotherapy by targeting IGF2BP3-induced NETosis in malignant glioma

Weiwei Dai, Ruotong Tian, Liubing Yu, Shasha Bian, Yuling Chen, Bowen Yin, Yuxuan Luan, Siqi Chen, Zhuoyang Fan, Rucheng Yan, Xin Pan, Yingyong Hou, Rong Li, Juxiang Chen () and Minfeng Shu ()
Additional contact information
Weiwei Dai: Fudan University
Ruotong Tian: Fudan University
Liubing Yu: Fudan University
Shasha Bian: Fudan University
Yuling Chen: Fudan University
Bowen Yin: Fudan University
Yuxuan Luan: Fudan University
Siqi Chen: Fudan University
Zhuoyang Fan: Fudan University
Rucheng Yan: Fudan University
Xin Pan: Fudan University
Yingyong Hou: Fudan University
Rong Li: Naval Medical University
Juxiang Chen: Naval Medical University
Minfeng Shu: Fudan University

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract Oncolytic virotherapy holds promise for cancer treatment, but the factors determining its oncolytic activity remain unclear. Neutrophil extracellular traps (NETs) are associated with cancer progression, yet their formation mechanism and role in oncolytic virotherapy remain elusive. In this study, we demonstrate that, in glioma, upregulation of IGF2BP3 enhances the expression of E3 ubiquitin protein ligase MIB1, promoting FTO degradation via the ubiquitin-proteasome pathway. This results in increased m6A-mediated CSF3 release and NET formation. Oncolytic herpes simplex virus (oHSV) stimulates IGF2BP3-induced NET formation in malignant glioma. In glioma models in female mice, a BET inhibitor enhances the oncolytic activity of oHSV by impeding IGF2BP3-induced NETosis, reinforcing virus replication through BRD4 recruitment with the CDK9/RPB-1 complex to HSV gene promoters. Our findings unveil the regulation of m6A-mediated NET formation, highlight oncolytic virus-induced NETosis as a critical checkpoint hindering oncolytic potential, and propose targeting NETosis as a strategy to overcome resistance in oncolytic virotherapy.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-44576-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44576-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-44576-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().