口服纳米递送一种肠道微生物代谢物增强 T 细胞干性以用于癌症免疫治疗

Gut microbial metabolites play crucial roles in regulating systemic immunity, but their mechanisms and limited drug-like properties remain unresolved.

Here we report an oral nano-formulation that leverages gut microbial metabolites to modulate T cell metabolism and amplify antitumour immunity. Through an in vitro screening of gut microbial metabolites, we identified 3,4-dihydroxybenzoic acid that improved adoptive T cell therapy and enhanced CD8 + T cell stemness by suppressing glycolysis and regulating the Akt-mTORC1-Myc pathway. To harness the potency of 3,4-dihydroxybenzoic acid for systemic cancer immunotherapy, we engineered a 3,4-dihydroxybenzoic acid prodrug nano-emulsion, significantly increasing its oral absorption and half-life.

In multiple murine tumour models, the oral nano-emulsion enhanced the expansion of antigen-specific, stem-like CD8 + T cells, sensitizing tumours to anti-PD-1 blockade and exerting robust antitumour efficacy. By integrating nanotechnology with microbial-metabolite-based immunotherapy, this study establishes a mechanistic link between the gut microbiota and T cell immunity, offering a promising approach for cancer immunotherapy.