Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity

Shuo Wang, An Song, Jun Xie, Yuan-Yuan Wang, Wen-Da Wang, Meng-Jie Zhang, Zhi-Zhong Wu, Qi-Chao Yang, Hao Li, Junjie Zhang () and Zhi-Jun Sun ()
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Shuo Wang: Wuhan University
An Song: Wuhan University
Jun Xie: Wuhan University
Yuan-Yuan Wang: Wuhan University
Wen-Da Wang: Wuhan University
Meng-Jie Zhang: Wuhan University
Zhi-Zhong Wu: Wuhan University
Qi-Chao Yang: Wuhan University
Hao Li: Wuhan University
Junjie Zhang: Wuhan University
Zhi-Jun Sun: Wuhan University

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Oncolytic viruses (OVs) show promise as a cancer treatment by selectively replicating in tumor cells and promoting antitumor immunity. However, the current immunogenicity induced by OVs for tumor treatment is relatively weak, necessitating a thorough investigation of the mechanisms underlying its induction of antitumor immunity. Here, we show that HSV-1-based OVs (oHSVs) trigger ZBP1-mediated PANoptosis (a unique innate immune inflammatory cell death modality), resulting in augmented antitumor immune effects. Mechanistically, oHSV enhances the expression of interferon-stimulated genes, leading to the accumulation of endogenous Z-RNA and subsequent activation of ZBP1. To further enhance the antitumor potential of oHSV, we conduct a screening and identify Fusobacterium nucleatum outer membrane vesicle (Fn-OMV) that can increase the expression of PANoptosis execution proteins. The combination of Fn-OMV and oHSV demonstrates potent antitumor immunogenicity. Taken together, our study provides a deeper understanding of oHSV-induced antitumor immunity, and demonstrates a promising strategy that combines oHSV with Fn-OMV.

Date: 2024
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DOI: 10.1038/s41467-024-48032-7

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