Summary of project PR000939
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 PR000939. The data can be accessed directly via it's Project DOI: 10.21228/M89T1B This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR000939 |
| Project DOI: | doi: 10.21228/M89T1B |
| Project Title: | Targeting Sirt2 reprograms T cell metabolism for effective immune response |
| Project Type: | Targeted Metabolomics |
| Project Summary: | There is a growing evidence that metabolism is a key driver of T cell functions. A switch from oxidative phosphorylation to aerobic glycolysis is a hallmark of T cell activation and is required to meet metabolic demands of proliferation and effector functions. However the mechanisms underlying the metabolic switch in T cells remain unclear. Here we identify Sirt2 as a crucial immune checkpoint coordinating metabolic and functional fitness of T cells. Sirt2 is induced upon T cells activation and increases in late maturation stages. Sirt2 negatively regulates glycolysis by targeting key glycolytic enzymes. Remarkably, Sirt2 knockout T cells exhibit profound upregulation of aerobic glycolysis with enhanced proliferation and effector function and thus effectively reject tumor challenge in vivo. Furthermore pharmacologic inhibition of Sirt2 in human tumor infiltrating lymphocytes demonstrated similar phenotype. Taken together our results demonstrate Sirt2 as an actionable target to reprogram T cell metabolism to augment immunotherapy. |
| Institute: | Moffitt Cancer Center |
| Department: | Immunology |
| Laboratory: | Sungjune Kim |
| Last Name: | Koomen |
| First Name: | John |
| Address: | 12902 Magnolia Drive |
| Email: | john.koomen@moffitt.org |
| Phone: | 8137458524 |
| Contributors: | Imene Hamaidi1, Lin Zhang2, Nayoung Kim3, Min Hsuan Wang1, Cristina Iclozan1, Bin Fang4, Min Liu4, John Koomen4, Anders Berglund5, Sungjune Kim1,6* |
Summary of all studies in project PR000939
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001373 | Targeting Sirt2 reprograms T cell metabolism for effective immune response | Mus musculus | Moffitt Cancer Center | MS* | 2021-01-25 | 1 | 9 | Uploaded data (2.3G)* |
