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

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
02 Jan 2024
Historique:
received: 22 06 2023
accepted: 20 12 2023
medline: 4 1 2024
pubmed: 4 1 2024
entrez: 3 1 2024
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-023-44576-2 PMID: 38167409
pubmed: 38167409
doi: 10.1038/s41467-023-44576-2
pii: 10.1038/s41467-023-44576-2
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

131

Subventions

Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : No. 81872467 and 82073880

Informations de copyright

© 2024. The Author(s).

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Auteurs

Weiwei Dai (W)

Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Ruotong Tian (R)

Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Liubing Yu (L)

Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Shasha Bian (S)

Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
ORCID: 0000-0002-7095-0867

Yuling Chen (Y)

Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Bowen Yin (B)

Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Yuxuan Luan (Y)

Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Siqi Chen (S)

Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Zhuoyang Fan (Z)

Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Interventional Radiology, Zhongshan hospital, Fudan University, Shanghai, China.

Rucheng Yan (R)

Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.

Xin Pan (X)

School of Basic Medical Sciences, Fudan University, Shanghai, China.
Nanhu Laboratory, National Center of Biomedical Analysis, Beijing, China.
ORCID: 0000-0002-1982-2261

Yingyong Hou (Y)

Department of Pathology, Zhongshan hospital, Fudan University, Shanghai, China.

Rong Li (R)

Department of Neurosurgery, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China.

Juxiang Chen (J)

Department of Neurosurgery, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China. juxiangchen@smmu.edu.cn.

Minfeng Shu (M)

Department of Pharmacology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. minfeng_shu@fudan.edu.cn.
Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China. minfeng_shu@fudan.edu.cn.
ORCID: 0000-0003-0514-1892

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