broad-scale environmental context | mouse digestive system |
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collection date | not provided |
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environmental medium | feces |
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geographic location | not provided |
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investigation type | metagenome-assembled genome |
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isolation source | mouse gut metagenome |
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project name | A growing body of evidence supports the notion that the gut microbiome plays an important role in cancer immunity. However, the underpinning mechanisms remain to be fully elucidated. One attractive hypothesis envisages that among the T cells elicited by the plethora of microbiome proteins a few exist that incidentally recognize neo-epitopes arising from cancer mutations (molecular mimicry (MM) hypothesis). To support MM, the human probiotic Escherichia coli Nissle was engineered with the SIINFEKL epitope (OVA-E.coli Nissle) and orally administered to C57BL6 mice. The treatment with OVA-E.coli Nissle, but not with wild type E. coli Nissle, induced OVA-specific CD8+ T cells and inhibited the growth of tumors in mice challenged with B16F10 melanoma cells expressing OVA. The microbiome shotgun sequencing and the sequencing of TCRs from T cells recovered from both lamina propria and tumors provide evidence that the main mechanism of tumor inhibition is mediated by the elicitation at the intestinal site of cross-reacting T cells, which subsequently reach the tumor environment. Importantly, the administration of Outer Membrane Vesicles (OMVs) from engineered E. coli Nissle, as well as from E. coli BL21(DE3)DompA, carrying cancer-specific T cell epitopes also elicited epitope-specific T cells in the intestine and inhibited tumor growth. Overall, our data strengthen the important role of MM in tumor immunity and assign a novel function of OMVs in host-pathogen interaction. Moreover, our results pave the way to the exploitation of probiotics and OMVs engineered with tumor specific-antigens as personalized mucosal cancer vaccines. |
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sample name | SRR19759419_bin.49_metawrap_v1.3_MAG |
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ENA-CHECKLIST | ERC000047 |
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ENA-FIRST-PUBLIC | 2022-12-13 |
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ENA-LAST-UPDATE | 2022-12-13 |
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External Id | SAMEA112223248 |
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INSDC center alias | EMG |
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INSDC center name | EMG |
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INSDC first public | 2022-12-13T16:27:12Z |
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INSDC last update | 2022-12-13T16:27:12Z |
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INSDC status | public |
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Submitter Id | SRR19759419_bin.49_metawrap_v1.3_MAG |
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assembly quality | Many fragments with little to no review of assembly other than reporting of standard assembly statistics |
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assembly software | metaSPAdes v3.15.3 |
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binning parameters | MaxBin2, MetaBat2, Concoct with default parameter of the metaWRAP pipeline. Bin refinement module used from metaWRAP with default parameters. |
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binning software | metawrap v1.3 |
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broker name | EMG broker account, EMBL-EBI |
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completeness score | 98.3 |
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completeness software | CheckM |
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contamination score | 0.0 |
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geographic location (latitude) | not provided |
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geographic location (longitude) | not provided |
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local environmental context | digestive tube |
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metagenomic source | mouse gut metagenome |
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sample derived from | SAMN29213142 |
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sequencing method | Illumina NovaSeq 6000 |
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taxonomic classification | The taxonomy of this metagenome-assembled genome was originally computed with GTDBtk, which assigned the following taxonomic annotation: d__Bacteria;p__Bacteroidetes;c__Bacteroidia;o__Bacteroidales;f__Muribaculaceae;g__Muribaculum;s__Muribaculum intestinale |
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taxonomic identity marker | multi-marker approach |
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