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.

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
Study IDST001373
Study TitleTargeting Sirt2 reprograms T cell metabolism for effective immune response
Study TypeTargeted Metabolomics
Study SummaryThere 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
DepartmentImmunology
LaboratorySungjune Kim
Last NameKoomen
First NameJohn
Address12902 Magnolia Drive
Emailjohn.koomen@moffitt.org
Phone8137458524
Submit Date2019-07-24
Num Groups2
Total Subjects9
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2021-01-25
Release Version1
John Koomen John Koomen
https://dx.doi.org/10.21228/M89T1B
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:


Treatment:

Treatment ID:TR001462
Treatment 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.
Treatment:anti-CD3 stimulation
Treatment Compound:antibody
Treatment Route:Cells placed on coated plate
Treatment Doseduration:72 hours
  logo