{
  "abstract": "Background Colorectal cancer (CRC) is the third leading cause of death in the US and is increasing globally. The microbiota is a driver of CRC pathogenesis, however, there are few microbes that are known to restrain CRC.Methods Using transplantation of the microbiota from patients with or without CRC into germfree mice, we found that the microbiota harbored by non-diseased individuals reduced tumor formation, and we identified Bacteriodes uniformis as protective.Results and Conclusions Proactive treatment with B. uniformis slowed tumor growth in mice and increased tumor infiltrating T and Natural Killer (NK) cells, by single cell sequencing and flow cytometry. Surprisingly, NK cells, but not T-cells, were required for B. uniformis-mediated protection and B. uniformis directly upregulated NK effectors. CRC is recalcitrant to immunotherapies for unknown reasons; however, we also show that animals colonized with CRC microbiotas failed to respond to a-CTLA-4 treatment, and addition of B. uniformis restores this response, which is dependent on NK cells. We further identified that a specific B. uniformis polysaccharide capsule molecule was essential for the tumor protection and NK activation, thus identifying the relevant immunomodulatory molecule. Taken together, we have determined that healthy individuals possess tumor suppressor microbes that prevent cancer by enhancing NK immunosurveillance and anti-tumor immunity via their capsule molecules.",
  "authors": [
    {
      "affiliations": [
        "The University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "Allison M Weis"
    },
    {
      "affiliations": [
        "The University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "Kaylyn Bauer"
    },
    {
      "affiliations": [
        "The University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "Neli Ulrich"
    },
    {
      "affiliations": [
        "The University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "Ryan O’Connell"
    },
    {
      "affiliations": [
        "The University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "William Tang"
    },
    {
      "affiliations": [
        "The University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "Zac Stephens"
    },
    {
      "affiliations": [
        "The University of Utah, Salt Lake City, UT, USA"
      ],
      "name": "June Round"
    }
  ],
  "title": "1137 A human-derived bacterium’s capsular polysaccharide activates a Lag-3-NK cell axis to restrain colon cancer and augment immunotherapy",
  "uid": "1ef0bd72-5d02-5eaa-885a-adead398a145"
}