Summary of project PR002273
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 PR002273. The data can be accessed directly via it's Project DOI: 10.21228/M8TC2W This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002273 |
| Project DOI: | doi: 10.21228/M8TC2W |
| Project Title: | Tumour interstitial fluid-enriched phosphoethanolamine suppresses T cell function |
| Project Summary: | Nutrient stress represents a significant barrier for antitumor immunity, and tumor interstitial fluid (TIF) often contains metabolites that hinder immune function. However, it is difficult to isolate the effects of tumor nutrient stress from other suppressive factors. Thus, we employed a chemically-defined cell culture medium based on the metabolomic profile of TIF: Tumor Interstitial Fluid Medium (TIFM). Culture of CD8+ T cells in TIFM limited cell expansion and impaired CD8+ T cell effector functions upon restimulation, suggesting tumor nutrient stress alone is sufficient to drive T cell dysfunction. We identified phosphoethanolamine (pEtn), a phospholipid intermediate, as a driver of T cell dysfunction. pEtn dampened T Cell Receptor (TCR) signaling by depleting T cells of diacylglycerol required for TCR signal transduction. Reduction of pEtn accumulation in tumors improved intratumoral T cell function and tumor control, suggesting pEtn accumulation plays a dominant role in TME immunosuppression. |
| Institute: | University of Chicago |
| Department: | Comprehensive Cancer Center |
| Laboratory: | UCCC-Metabolomics Platform |
| Last Name: | Shah |
| First Name: | Hardik |
| Address: | 900 E 57th street, Chicago, IL, 60637, USA |
| Email: | hardikshah@uchicago.edu |
| Phone: | 7738348830 |
Summary of all studies in project PR002273
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003664 | Tumour interstitial fluid-enriched phosphoethanolamine suppresses T cell function. | Mus musculus | University of Chicago | MS | 2025-01-20 | 1 | 100 | Uploaded data (4.9G)* |