Summary of project PR002027
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 PR002027. The data can be accessed directly via it's Project DOI: 10.21228/M8M24P This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002027 |
| Project DOI: | doi: 10.21228/M8M24P |
| Project Title: | Malic Enzyme 2 maintains metabolic state and anti-tumor immunity of CD8+ T cells |
| Project Summary: | The functional integrity of CD8+ T cells is closely linked to metabolic reprogramming, therefore, understanding of the metabolic basis of CD8+ T cell activation and antitumor immunity could provide insights into tumor immunotherapy. Here, we report that ME2 is critical for CD8+ T cell activation and immune response against malignancy. ME2 deficiency suppresses CD8+ T cells activation and anti-tumor immune response in vitro and in vivo. Mechanistically, ME2 depletion blocks the TCA cycle flux, leading to the accumulation of fumarate. Fumarate directly binds to DAPK1 and inhibits its activity by competing with ATP for binding. Notably, ME2 deficiency increases the ratio of fumarate to ATP, thereby leading to the inhibition of DAPK1. Consistently, pharmacological inhibition of DAPK1 abolishes the anti-tumor function conferred by ME2 to CD8+ T cells. Collectively, these findings demonstrate a role for ME2 in the regulation of CD8+ T cell metabolism and effector functions, as well as an unexpected function for fumarate as a metabolic signal in the inhibition of DAPK1. |
| Institute: | Peking Union Medical College |
| Last Name: | zhenxi |
| First Name: | zhang |
| Address: | Beijing Dongdan Santiao No.5 |
| Email: | 13121716766@163.com |
| Phone: | 010-69156953 |
Summary of all studies in project PR002027
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003265 | Malic Enzyme 2 maintains metabolic state and anti-tumor immunity of CD8+ T cells | Mus musculus | Peking Union Medical College | MS | 2024-07-15 | 1 | 16 | Uploaded data (1.3G)* |
