Modulating tumor immunity using advanced microbiome therapeutics producing an indole metabolite.

ABSTRACT: The gut microbiome has emerged as a key player in modulating immune responses against cancer, suggesting that microbial interventions can enhance treatment outcomes. Indole metabolites produced by probiotic bacteria activate the aryl hydrocarbon receptor (AhR), a transcription factor important for immune cell regulation. Cancer patients with high plasma concentrations of these metabolites have shown improved survival. Building on these findings, we have engineered Escherichia coli Nissle 1917 to produce the AhR agonist indole-3-acetic acid. Delivery of indole-3-acetic acid by tumor-colonizing bacteria changes the tumor microenvironment in a murine model, significantly increasing levels of CXCL9 and IFN-γ and elevating tumor-infiltrating T-cell abundance and activation. Treatment with our e

SUBMITTER: Vaaben TH 

PROVIDER: S-EPMC11977207 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature