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         headline:Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice
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      headline:Bifidobacterium bifidum strains synergize with immune checkpoint inhibitors to reduce tumour burden in mice
      description:The gut microbiome can influence the development of tumours and the efficacy of cancer therapeutics1–5; however, the multi-omics characteristics of antitumour bacterial strains have not been fully elucidated. In this study, we integrated metagenomics, genomics and transcriptomics of bacteria, and analyses of mouse intestinal transcriptome and serum metabolome data to reveal an additional mechanism by which bacteria determine the efficacy of cancer therapeutics. In gut microbiome analyses of 96 samples from patients with non-small-cell lung cancer, Bifidobacterium bifidum was abundant in patients responsive to therapy. However, when we treated syngeneic mouse tumours with commercial strains of B. bifidum to establish relevance for potential therapeutic uses, only specific B. bifidum strains reduced tumour burden synergistically with PD-1 blockade or oxaliplatin treatment by eliciting an antitumour host immune response. In mice, these strains induced tuning of the immunological background by potentiating the production of interferon-γ, probably through the enhanced biosynthesis of immune-stimulating molecules and metabolites. An analysis of gut microbiomes of patients with non-small-cell lung cancer reveals an association between Bifidobacterium bifidum abundance and response to cancer therapy. In murine models of syngeneic tumours, administration of commercial B. bifidum strains synergizes with immune checkpoint blockade to reduce tumour burden, but the therapeutic potential of B. bifidum is affected by strain-level variation.
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