Sustained nitric oxide production by engineered E. coli remodels the tumor microenvironment and potentiates immunotherapy - PubMed
3 hours ago
- #Nitric Oxide
- #Tumor Microenvironment
- #Immunotherapy
- Engineered E. coli Nissle 1917 (ECN-NO) produces sustained nitric oxide (NO) to remodel the tumor microenvironment (TME).
- The synthetic arginine-NO circuit enhances arginine biosynthesis and NO production by deleting ArgR and co-expressing ArgG/ArgH with BsNOS.
- ECN-NO colonization in tumors improves anti-PD-L1 immunotherapy efficacy, leading to durable regression in multiple solid tumor models.
- Mechanistically, ECN-NO normalizes vasculature, recruits dendritic cells, alleviates immunosuppression, and expands functional CD8+ T cells.
- The therapy reverses T cell exhaustion and promotes memory T cell formation, sustaining antitumor immunity for over 120 days.