PXD048393

PXD048393 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-10 11:37:03	ID requested
⏵ 1	2024-05-20 12:52:05	announced

10.1016/J.CMET.2024.02.009;

submitter keyword: metabolism, lipid,T cell, endoplasmic reticulum, immunotherapy, mitochondria, tumor microenvironment

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

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/2024/05/PXD048393

PRIDE project URI

• PRIDE
  1. PXD048393
     1. Label: PRIDE project
     2. Name: Acetyl-CoA Carboxylase Obstructs CD8+ T-Cell Lipid Utilization in the Tumor Microenvironment