PXD012796

PXD012796 is an original dataset announced via ProteomeXchange.

Title	Sirt2 inhibition reprograms T cell metabolism for optimal anti-tumor immunity: Lysine Acetylation
Description	Growing evidence indicates 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 cell 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 a similar phenotype. Taken together, our results demonstrate Sirt2 as an actionable target to reprogram T cell metabolism to augment immunotherapy.
HostingRepository	PRIDE
AnnounceDate	2020-06-15
AnnouncementXML	Submission_2020-08-11_22:44:34.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD012796
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	John Koomen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-20 03:54:46	ID requested
1	2020-06-15 02:55:45	announced
⏵ 2	2020-08-11 22:44:35	announced	2020-08-12: Updated publication reference for PubMed record(s): 32768387.

Hamaidi I, Zhang L, Kim N, Wang MH, Iclozan C, Fang B, Liu M, Koomen JM, Berglund AE, Yoder SJ, Yao J, Engelman RW, Creelan BC, Conejo-Garcia JR, Antonia SJ, Mul, é JJ, Kim S, Sirt2 Inhibition Enhances Metabolic Fitness and Effector Functions of Tumor-Reactive T Cells. Cell Metab, 32(3):420-436.e12(2020) [pubmed]

submitter keyword: Sirtuin 2, T cell, Metabolism, Glycolysis, Acetylation

Sungjune Kim, MD
contact affiliation	Departments of Immunology and Radiation Oncology Moffitt Cancer Center Tampa, FL, USA
contact email	sungjune.kim@moffitt.org
lab head
John Koomen
contact affiliation	Moffitt Cancer Center
contact email	john.koomen@moffitt.org
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/06/PXD012796

PRIDE project URI

• PRIDE
  1. PXD012796
     1. Label: PRIDE project
     2. Name: Sirt2 inhibition reprograms T cell metabolism for optimal anti-tumor immunity: Lysine Acetylation