PXD019763 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-06-15 02:48:56 | ID requested | |
⏵ 1 | 2020-06-16 00:53:16 | announced | |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD019763
- Label: PRIDE project
- Name: Sirt2 Inhibition Reprograms T Cell Metabolism to Confer Superior Anti-Tumor Immunity