⮝ Full datasets listing

PXD019763

PXD019763 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSirt2 Inhibition Reprograms T Cell Metabolism to Confer Superior Anti-Tumor Immunity
DescriptionDysregulated 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.
HostingRepositoryPRIDE
AnnounceDate2020-06-16
AnnouncementXMLSubmission_2020-06-16_00:53:15.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD019763
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterJohn Koomen
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListacetylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-06-15 02:48:56ID requested
12020-06-16 00:53:16announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Sirt2, Lysine Acetylation, T Cells, Anti-tumor Immunity, LC-MS/MS
Contact List
Sungjune Kim, MD/PhD
contact affiliationImmunology and Radiation Oncology Moffitt Cancer Center Tampa, FL, USA
contact emailsungjune.kim@moffitt.org
lab head
John Koomen
contact affiliationMoffitt Cancer Center
contact emailjohn.koomen@moffitt.org
dataset submitter
Full Dataset Link List
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
Repository Record List
[ + ]