Summary of Study ST002217

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001416. The data can be accessed directly via it's Project DOI: 10.21228/M8PM6K This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002217
Study TitleNon-targeted metabolomics screen comparing metabolite profiles of serum from PDAC-bearing mice that received 1% choline supplementation or control diet using high-resolution, high-performance LC-MS/MS analysis.
Study SummaryThe composition of the gut microbiome controls innate and adaptive immunity and has emerged as a key regulator of tumor growth and the success of immune checkpoint blockade (ICB) therapy. However, the underlying mechanisms remain unclear. Pancreatic ductal adenocarcinoma (PDAC) tends to be refractory to therapy, including ICB. We found that the gut microbe-derived metabolite trimethylamine N-oxide (TMAO) enhances anti-tumor immunity to PDAC. Delivery of TMAO given intraperitoneally or via dietary choline supplement to PDAC-bearing mice reduces tumor growth and is associated with an immunostimulatory tumor-associated macrophage (TAM) phenotype and activated effector T cell response in the tumor microenvironment. Mechanistically, TMAO signals through potentiating type-I interferon (IFN) pathway and confers anti-tumor effects in a type-I IFN dependent manner. Notably, delivering TMAOprimed macrophages alone produced similar anti-tumor effects. Combining TMAO with ICB (anti-PD1 and/or anti-Tim3) significantly reduced tumor burden and improved survival beyond TMAO or ICB alone. Finally, the levels of trimethylamine (TMA)- producing bacteria and of CutC gene expression correlate with improved survivorship and response to anti-PD1 in cancer patients. Together, our study identifies the gut microbial metabolite TMAO as an important driver of anti-tumor immunity and lays the groundwork for new therapeutic strategies.
Institute
The Wistar Institute
Last NameShinde
First NameRahul
Address3601 Spruce St, Philadelphia, PA 19104
Emailrshinde@wistar.org
Phone215-898-3717
Submit Date2022-07-11
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2022-07-22
Release Version1
Rahul Shinde Rahul Shinde
https://dx.doi.org/10.21228/M8PM6K
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Sample Preparation:

Sampleprep ID:SP002309
Sampleprep Summary:Briefly, polar metabolites were extracted from serum samples with 10 times volume of ice-cold 80% methanol. Deproteinated supernatants were stored at -80 °C prior to analysis. A quality control (QC) sample was generated by pooling equal volumes of all samples immediately before LC-MS analysis.
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