4.8 Article

A defined commensal consortium elicits CD8 T cells and anti-cancer immunity

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NATURE
卷 565, 期 7741, 页码 600-+

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NATURE PUBLISHING GROUP
DOI: 10.1038/s41586-019-0878-z

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资金

  1. AMED LEAP [JP18gm0010003]
  2. Takeda Science Foundation
  3. Mitsubishi Foundation
  4. AMED PRIME [JP18gm6010013]
  5. Nakajima Foundation
  6. NIH [DK43351, AT009708]
  7. Center for Microbiome Informatics and Therapeutics, MIT

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There is a growing appreciation for the importance of the gut microbiota as a therapeutic target in various diseases. However, there are only a handful of known commensal strains that can potentially be used to manipulate host physiological functions. Here we isolate a consortium of 11 bacterial strains from healthy human donor faeces that is capable of robustly inducing interferon-gamma-producing CD8 T cells in the intestine. These 11 strains act together to mediate the induction without causing inflammation in a manner that is dependent on CD103(+) dendritic cells and major histocompatibility (MHC) class Ia molecules. Colonization of mice with the 11-strain mixture enhances both host resistance against Listeria monocytogenes infection and the therapeutic efficacy of immune checkpoint inhibitors in syngeneic tumour models. The 11 strains primarily represent rare, low-abundance components of the human microbiome, and thus have great potential as broadly effective biotherapeutics.

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