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Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells
Published on: August 1, 2025
Metabolic Reprogramming by Engineered Probiotics Potentiates Tumor Chemodynamic Immunotherapy
Kai Zhang1, Hongyang Li2, Zhaoyu Ma1
1School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore, Singapore.
Advanced Materials (Deerfield Beach, Fla.)
|July 31, 2026
Summary
Engineered bacteria reprogram the tumor microenvironment by producing metabolites like leucine. This metabolic reprogramming enhances anti-cancer immunity by modulating neutrophils and immune cells, improving therapy efficacy.
Area of Science:
- Microbiology
- Immunology
- Biotechnology
Background:
- Engineered bacteria can remodel immunosuppressive tumor microenvironments.
- Bacterial metabolites are key mediators in interkingdom crosstalk but their roles are underexplored.
- Targeting tumor metabolism is a promising strategy for cancer immunotherapy.
Purpose of the Study:
- To develop a programmable probiotic platform using Lactobacillus gasseri (LG) for bladder cancer therapy.
- To investigate the metabolic interplay between LG and the tumor microenvironment.
- To elucidate the mechanisms by which bacterial metabolites modulate the immune response.
Main Methods:
- Engineered Lactobacillus gasseri (LG) strain for tumor colonization and metabolite production.
- Utilized hemoglobin-modified MnOx nanoparticles for enhanced chemodynamic therapy.
- Analyzed neutrophil phenotypic reprogramming via microbial metabolites, including L-leucine.
- Assessed immune cell populations and functions including dendritic cells, macrophages, CD8+ T cells, and NK cells.
Main Results:
- The engineered LG strain demonstrated superior tumor colonization and produced H2O2/lactate.
- Microbial metabolites, particularly L-leucine, reprogrammed neutrophils, suppressing pro-angiogenic and activating antigen-presenting subsets.
- The system induced coordinated immunomodulation: dendritic cell maturation, increased CD74+ neutrophils, M1 macrophage polarization, and enhanced CD8+ T cell and NK cell infiltration.
- Bacteria-tumor metabolic crosstalk upregulated beneficial metabolites, bridging innate metabolic regulation with adaptive antitumor immunity.
Conclusions:
- Engineered Lactobacillus gasseri can reprogram the tumor microenvironment through metabolic crosstalk.
- L-leucine plays a crucial role in neutrophil phenotypic reprogramming, enhancing anti-tumor immunity.
- This metabolism-centric framework offers a novel strategy for bacteria-mediated cancer immunotherapy, moving beyond material-centric approaches.
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