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Engineered bacteria reprogram tumor microenvironment via cell senescence and neutrophil extracellular traps

Wanfa Dong1, Chenyang Li2, Jiqiang Lu1

  • 1School of Biopharmacy, China Pharmaceutical University, Nanjing 211198, China.

Acta Pharmaceutica Sinica. B
|April 27, 2026
PubMed

Insights

Attenuated Salmonella (VNP) shows anti-cancer promise by inducing cellular senescence. A new VNP variant, VNP-SNase, targets neutrophil extracellular traps (NETs), enhancing anti-tumor immunity and improving cancer treatment safety and efficacy.

Area of Science:

  • Oncology
  • Microbiology
  • Immunology

Background:

  • Attenuated Salmonella VNP20009 (VNP) exhibits anti-cancer properties.
  • The precise anti-tumor mechanisms of VNP, particularly the role of cellular senescence, require further elucidation.
  • Cellular senescence is implicated in tumor progression, but its specific involvement in VNP therapy is unclear.

Purpose of the Study:

  • To investigate the role of cellular senescence in VNP-mediated anti-tumor effects.
  • To explore the paradoxical role of VNP-induced senescence in promoting neutrophil extracellular traps (NETs).
  • To engineer a VNP variant (VNP-SNase) to overcome NETs-mediated tumor promotion and enhance anti-cancer efficacy.

Main Methods:

  • Utilized attenuated Salmonella VNP20009 for anti-tumor studies.
  • Investigated VNP-induced cellular senescence in tumor and vascular endothelial cells.
  • Engineered VNP-SNase to release Staphylococcus aureus nuclease for DNA degradation.
  • Assessed NETs formation, anti-tumor immunity, and tumor suppression in various tumor models.

Main Results:

  • VNP induced cellular senescence, leading to anti-tumor growth and anti-angiogenesis.
  • VNP-induced senescence promoted NETs formation, paradoxically enhancing tumor progression.
  • VNP-SNase effectively inhibited NETs formation across multiple tumor types.
  • VNP-SNase demonstrated enhanced anti-tumor immunity and improved tumor suppression with better biosafety.

Conclusions:

  • Cellular senescence plays a critical role in VNP therapy, with both beneficial and detrimental effects.
  • Targeting NETs formation is a crucial strategy to enhance the efficacy of Salmonella-based cancer therapies.
  • VNP-SNase represents a promising next-generation therapeutic agent for cancer treatment.
Keywords:
Cancer immunotherapyCellular senescenceNETosisNeutrophilOncolytic bacteriaStaphylococcal nucleaseT cell exhaustionVNP20009

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