Intratumoral immune-microbial crosstalk shaped by tumor cell-derived extracellular vesicles encapsulating berberine boosts lung cancer immunotherapy

drug screening assays, berberine was identified as a promising agent that selectively inhibits harmful bacteria while sparing beneficial ones. To address berberine's low solubility and tumor targeting issues, it was encapsulated into tumor cell-derived extracellular vesicles (EV-ber). Feature analysis demonstrated that EV-ber shifted the intratumoral microbiome profile toward an anti-tumor phenotype and enhanced anti-tumor immunity in the TME. Furthermore, EV-ber administration inhibited LUAD growth, impaired LUAD metastatic ability, and boosted the effectiveness of anti-PD-L1 immunotherapy in mouse models. In conclusion, this work demonstrates the potential of personalized intratumoral microbial re-education strategies in LUAD therapy.