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

Nat Commun. 2024 Apr 30;15(1):3669. doi: 10.1038/s41467-024-48032-7.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • Fusobacterium nucleatum* / immunology
  • Herpesvirus 1, Human* / genetics
  • Herpesvirus 1, Human* / immunology
  • Humans
  • Immunity, Innate
  • Mice
  • Mice, Inbred BALB C
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Oncolytic Virotherapy* / methods
  • Oncolytic Viruses* / genetics
  • Oncolytic Viruses* / immunology
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / immunology
  • RNA-Binding Proteins* / metabolism


  • RNA-Binding Proteins