Summary of Study ST001373
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
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
Study ID | ST001373 |
Study Title | Targeting Sirt2 reprograms T cell metabolism for effective immune response |
Study Type | Targeted Metabolomics |
Study 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 |
john.koomen@moffitt.org | |
Phone | 8137458524 |
Submit Date | 2019-07-24 |
Num Groups | 2 |
Total Subjects | 9 |
Raw Data Available | Yes |
Raw Data File Type(s) | raw(Thermo) |
Analysis Type Detail | LC-MS |
Release Date | 2021-01-25 |
Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Collection:
Collection ID: | CO001442 |
Collection Summary: | CD8+ purified T cells from WT (n = 5) and Sirt2 KO (n = 4) mouse spleens were stimulated with plate-coated anti-CD3 (5 μg/ml, BXCELL) for 72h, followed by extensive washing of the cell pellets with PBS. All processes are carried out on ice. An aliquot (1 mL) of 80% MeOH extraction solvent is added to the sample (with Internal Standards spiked in) for protein precipitation. The 80% MeOH extraction solvent is is precooled to -80C for at least one hour. After addition of the extraction solvent, the samples are then placed in the -80C freezer for 30 minutes. After incubation, the samples are immediately centrifuged at 18,800 × g (Microfuge 22R, Beckman Coulter) at 4 C for 10 minutes. After centrifugation, the supernatant is transferred to new a microcentrifuge tube (Eppendorf brand) for drying by vacuum concentration. The dried metabolites are re-dissolved in 80% MeOH. The precipitated protein pellet is resolubilized for Bradford assays to measure the protein concentration as a quality control for the sample loading. |
Sample Type: | Spleen |
Collection Method: | T-cell isolation |
Collection Location: | Moffitt Cancer Center |
Collection Frequency: | 1 time |
Volumeoramount Collected: | 2,000,000 cells |
Storage Conditions: | -80℃ |