PXD019763

PXD019763 is an original dataset announced via ProteomeXchange.

Title	Sirt2 Inhibition Reprograms T Cell Metabolism to Confer Superior Anti-Tumor Immunity
Description	Dysregulated metabolism is a key driver of maladaptive tumor-reactive T lymphocytes within the tumor microenvironment (TME). Actionable mechanisms that rescue the effector activity of anti-tumor T cells in a metabolically restricted TME remain elusive. Here, we report that the Sirtuin-2 (Sirt2) protein deacetylase functions as a master metabolic checkpoint that inhibits T cell metabolic fitness and impairs T cell effector functions and anti-tumor immunity. Mechanistically, Sirt2 suppresses glycolysis and oxidative-phosphorylation (OxPhos) by deacetylating key enzymes involved in glycolysis, tricarboxylic acid (TCA)-cycle, fatty acid oxidation (FAO) and glutaminolysis. Accordingly, Sirt2-deficient T cells exhibit a hyper-metabolic activity with increased glycolysis and OxPhos, resulting in enhanced proliferation and effector functions at tumor beds and subsequently exhibiting superior anti-tumor activity. Importantly, pharmacologic inhibition of Sirt2 endows human lung tumor-infiltrating lymphocytes (TILs) with these superior metabolic fitness and enhanced effector functions. Furthermore, upregulation of Sirt2 expression in human TILs negatively correlates with response to Nivolumab and TIL therapy in non-small cell lung cancer (NSCLC). Our findings unveil Sirt2 as an unexpected actionable target for reprogramming T cell metabolism to augment a broad spectrum of cancer immunotherapies.
HostingRepository	PRIDE
AnnounceDate	2020-06-16
AnnouncementXML	Submission_2020-06-16_00:53:15.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD019763
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	acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-15 02:48:56	ID requested
⏵ 1	2020-06-16 00:53:16	announced

Dataset with its publication pending

submitter keyword: Sirt2, Lysine Acetylation, T Cells, Anti-tumor Immunity, LC-MS/MS

Sungjune Kim, MD/PhD
contact affiliation	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/PXD019763

PRIDE project URI

• PRIDE
  1. PXD019763
     1. Label: PRIDE project
     2. Name: Sirt2 Inhibition Reprograms T Cell Metabolism to Confer Superior Anti-Tumor Immunity