Summary of project PR001416
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
| Project ID: | PR001416 |
| Project DOI: | doi: 10.21228/M8PM6K |
| Project Title: | The microbiome-derived metabolite TMAO drives immune activation and boosts response to immune checkpoint blockade in pancreatic cancer |
| Project Summary: | The 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 Name: | Shinde |
| First Name: | Rahul |
| Address: | 3601 Spruce St, Philadelphia, PA 19104 |
| Email: | rshinde@wistar.org |
| Phone: | 215-898-3717 |
Summary of all studies in project PR001416
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002216 | Non-targeted metabolomics screen comparing metabolite profiles of serum from PDAC-bearing mice that received metronidazole using high-resolution, high-performance LC-MS/MS analysis. | Mus musculus | The Wistar Institute | MS | 2022-07-22 | 1 | 18 | Uploaded data (2.2G)* |
| ST002217 | Non-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. | Mus musculus | The Wistar Institute | MS | 2022-07-22 | 1 | 20 | Uploaded data (2.2G)* |
