Summary of project PR002747
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 PR002747. The data can be accessed directly via it's Project DOI: 10.21228/M8KG2R This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002747 |
| Project DOI: | doi: 10.21228/M8KG2R |
| Project Title: | Oxidative pentose phosphate pathway is required for T cell activation and anti-tumor immunity |
| Project Summary: | Glucose is catabolized by two major metabolic pathways, glycolysis and the oxidative pentose phosphate pathway (oxPPP). The oxPPP generates NADPH at two steps, glucose-6-phosphate dehydrogenase (G6PD), the most common enzyme deficiency in humans, and 6-phosphogluconate dehydrogenase (PGD). Previous literature suggests that G6PD supports but PGD limits T cell-mediated immunity. Here we use T cell-specific knockout mouse models to show that both enzymes are required for anti-tumor immunity and response to immunotherapy. PGD knockout depletes mature T cells systemically, while G6PD loss does not reduce basal T cell populations but results in apoptosis upon activation. Such apoptosis is not reversed by major downstream products of the oxPPP, including antioxidants, nucleosides, or fatty acids. Instead, T cells are partially rescued by removal of media cystine, whose reduction requires NADPH. G6PD loss induces an oxidative stress response that upregulates cystine import, which together with low NADPH leads to fatal disulfide stress. Overall, these results highlight an essential role for the oxidative pentose phosphate pathway in cystine homeostasis and T cell-mediated immunity. |
| Institute: | Princeton University |
| Last Name: | Chen |
| First Name: | Zihong |
| Address: | Carl Icahn Laboratory, South Drive, Princeton, New Jersey, 08544, USA |
| Email: | zihongc@princeton.edu |
| Phone: | 6099333507 |
Summary of all studies in project PR002747
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004333 | Oxidative pentose phosphate pathway is required for T cell activation and anti-tumor immunity - G6PD-knockout | Mus musculus | Princeton University | MS | 2025-11-28 | 1 | 13 | Uploaded data (442.3M)* |
| ST004334 | Oxidative pentose phosphate pathway is required for T cell activation and anti-tumor immunity - PGD-knockout | Mus musculus | Princeton University | MS | 2025-11-28 | 1 | 8 | Uploaded data (245.4M)* |
