Fusobacterium nucleatum-mediated tryptophan metabolic reprogramming facilitates immunosuppression and metastasis in triple-negative breast cancer

Fusobacterium nucleatum ( F. nucleatum ) is a prevalent Gram-negative anaerobic bacterium commonly found in the oral cavity. Recent studies have shown that F. nucleatum colonizes breast cancer by binding to Gal–GalNAc through the adhesin Fap2, but how they regulate the tumor microenvironment remains unknown. Here we observed an enrichment of F. nucleatum in triple-negative breast cancer (TNBC) relative to ER + and HER2 + breast cancer subtypes, and found that F. nucleatum promoted lung metastasis and immunosuppression in TNBC. Mechanistically, F. nucleatum promotes tryptophan metabolism in TNBC by up-regulating the tryptophan metabolic enzyme IL4I1 through the IL20–JAK–STAT4 signaling axis, thus inhibiting the effect of anti-PD-1 antibody immunotherapy and promoting lung metastasis and immunosuppression. Collectively, our findings shed light on the process by which F. nucleatum promotes lung metastasis and immunosuppression in TNBC, and provide evidence for finding new therapeutic targets and strategies for TNBC.