Summary of Study ST002216

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.

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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 IDST002216
Study TitleNon-targeted metabolomics screen comparing metabolite profiles of serum from PDAC-bearing mice that received metronidazole 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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Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Treatment
SA211899Control PDAC 4Control
SA211900Control PDAC 6Control
SA211901Control PDAC 8Control
SA211902Control PDAC 3Control
SA211903Control PDAC 7Control
SA211904Control PDAC 5Control
SA211905Control PDAC 2Control
SA211906Control PDAC 1Control
SA211907Metronidazole PDAC 1Metronidazole
SA211908Metronidazole PDAC 2Metronidazole
SA211909Metronidazole PDAC 5Metronidazole
SA211910Metronidazole PDAC 4Metronidazole
SA211911Metronidazole PDAC 3Metronidazole
SA211912QC-3n/a
SA211913QC-4n/a
SA211914QC-2n/a
SA211915QC-6n/a
SA211916QC-5n/a
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