biostudies-literatureLi WFundamental research program funding of Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of MedicineNational Natural Science Foundation of Chinae70070https://www.ebi.ac.uk/biostudies/studies/S-EPMC12003102biostudies-literatureUnknown14(4)Only a minority of patients with head and neck squamous cell carcinoma (HNSCC) respond favourably to immunotherapy. The oral oncogenic bacterium Fusobacterium nucleatum (F.nucleatum) was recently observed to suppress the anti-tumour immune response, although the mechanisms remain unclear. In this study, we found that outer membrane vesicles (OMVs) derived from F.nucleatum (F.n-OMVs) promoted HNSCC progression by inducing immunosuppressive phenotypes of tumour-associated macrophages (TAMs), resulting in decreased cytotoxic T lymphocyte infiltration in vivo. Mechanistically, TAMs internalized tryptophanase presented in F.n-OMVs, which activated the tryptophan-2,3-dioxygenase 2/aryl hydrocarbon receptor (TDO2/AHR) pathway and upregulated the transcription of immunosuppressive cytokines and imJournal of extracellular vesiclesFusobacterium nucleatum-Derived Outer Membrane Vesicles Promote Immunotherapy Resistance via Changes in Tryptophan Metabolism in Tumour-Associated Macrophages.PMC1200310282173217JYZZ1808223009082373352Li WYan MMao MZhang ZChen WWu RJi YWang XDou SfalseFusobacterium nucleatum-Derived Outer Membrane Vesicles Promote Immunotherapy Resistance via Changes in Tryptophan Metabolism in Tumour-Associated Macrophages.Only a minority of patients with head and neck squamous cell carcinoma (HNSCC) respond favourably to immunotherapy. The oral oncogenic bacterium Fusobacterium nucleatum (F.nucleatum) was recently observed to suppress the anti-tumour immune response, although the mechanisms remain unclear. In this study, we found that outer membrane vesicles (OMVs) derived from F.nucleatum (F.n-OMVs) promoted HNSCC progression by inducing immunosuppressive phenotypes of tumour-associated macrophages (TAMs), resulting in decreased cytotoxic T lymphocyte infiltration in vivo. Mechanistically, TAMs internalized tryptophanase presented in F.n-OMVs, which activated the tryptophan-2,3-dioxygenase 2/aryl hydrocarbon receptor (TDO2/AHR) pathway and upregulated the transcription of immunosuppressive cytokines and im2025-01-01T00:00:00Z2025 Apr2026-06-02T06:41:41.607Z2026-05-25T03:07:48.762ZS-EPMC120031024024123010.1002/jev2.70070