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.

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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
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

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Project:

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*
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