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Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity
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Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity
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Journal Article
Fn-OMV potentiates ZBP1-mediated PANoptosis triggered by oncolytic HSV-1 to fuel antitumor immunity
2024
Overview
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.
The potential of oncolytic virus (OV) for cancer therapy is limited by the efficiency of immune response induced. Here the authors show that HSV-1-based OV is capable of triggering ZBP1-mediated PANoptosis resulting in effective tumor growth inhibition.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ Animals
/ Cancer
/ Female
/ Fusobacterium nucleatum - immunology
/ Herpesvirus 1, Human - genetics
/ Herpesvirus 1, Human - immunology
/ Humanities and Social Sciences
/ Humans
/ Immunity
/ Mice
/ Oncolytic Virotherapy - methods
/ Oncolytic Viruses - genetics
/ Oncolytic Viruses - immunology
/ RNA-Binding Proteins - genetics
/ RNA-Binding Proteins - immunology
/ RNA-Binding Proteins - metabolism
/ Science
/ Tumors
