PXD048393 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Acetyl-CoA Carboxylase Obstructs CD8+ T-Cell Lipid Utilization in the Tumor Microenvironment |
Description | The solid tumor microenvironment (TME) imprints a compromised metabolic state in tumor infiltrating T cells (TILs) hallmarked by the inability to maintain effective energy synthesis for antitumor function and survival. T cells in the TME must catabolize lipids via mitochondrial fatty acid oxidation (FAO) to supply energy in nutrient stress, and it is established that T cells enriched in FAO are adept at cancer control. However, endogenous TILs and unmodified cellular therapy products fail to sustain bioenergetics in tumors. Using patient samples and mouse models, we reveal that the solid TME imposes perpetual acetyl-CoA carboxylase (ACC) activity, invoking lipid biogenesis and storage in TILs that directly opposes FAO. Using metabolic, lipidomic, and confocal imaging strategies, we find that restricting ACC rewires T cell metabolism, enabling energy maintenance in TME stress. Moreover, limiting ACC activity potentiates a gene and phenotypic program indicative of T cell longevity, engendering T cells with increased survival and polyfunctionality, with the ability to control solid cancer. |
HostingRepository | PRIDE |
AnnounceDate | 2024-05-20 |
AnnouncementXML | Submission_2024-05-20_12:52:05.114.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Katie Hurst |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-01-10 11:37:03 | ID requested | |
⏵ 1 | 2024-05-20 12:52:05 | announced | |
Publication List
Keyword List
submitter keyword: metabolism, lipid,T cell, endoplasmic reticulum, immunotherapy, mitochondria, tumor microenvironment |
Contact List
Jessica E. |
contact affiliation | Immunotherapy Program, Lineberger Comprehensive Cancer Center Department of Cell Biology & Physiology, University of North Carolina at Chapel Hill |
contact email | jess_thaxton@med.unc.edu |
lab head | |
Katie Hurst |
contact affiliation | University of North Carolina at Chapel Hill |
contact email | katie_hurst@med.unc.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD048393
- Label: PRIDE project
- Name: Acetyl-CoA Carboxylase Obstructs CD8+ T-Cell Lipid Utilization in the Tumor Microenvironment