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PXD052688

PXD052688 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe Prostacyclin Receptor is a NRF2-regulated Immune Checkpoint in CD8 T cells
DescriptionImmune checkpoint inhibitor (ICI) therapies revitalize anti-cancer responses by intercepting protein-protein interactions between exhausted CD8 T (Tex) cells and cancer cells (e.g. PD-1:PD-L1). However, up to 50% of patients receiving ICIs relapse, warranting further interrogation of the underpinnings of Tex. We conducted RNA-seq meta-analysis of Tex versus effector (Teff) mouse CD8 T cells, and highlighted NRF2 transcriptional targets as the most upregulated gene set in Tex cells. LCMV or cancer inoculation of mice bearing NRF2 hyperactive—or Keap1-/- (NRF2 negative regulator)—T cells demonstrated that NRF2 drives Tex; evidenced by increased co-inhibitory marker (PD-1/TIM-3) expression and reduced cytokine (IFN-g/Granzyme-B) production. RNA-seq of Keap1-/- highlight Ptgir—which encodes the prostacyclin lipid receptor— as the most upregulated gene versus WT T cells. Accordingly, PTGIR knockout in NRF2-hyperactive/ Tex cells decreased PD-1/TIM-3 expression, increased cytokine production, and attenuated tumor growth. Our data underscore PTGIR as a NRF2-regulated Tex driver and illuminate an unconventional immune checkpoint class potentially based on protein-lipid interactions
HostingRepositoryPRIDE
AnnounceDate2025-04-25
AnnouncementXMLSubmission_2025-04-25_12:55:59.811.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHyoungjoo Lee
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListNo PTMs are included in the dataset
InstrumentOrbitrap Eclipse
Dataset History
RevisionDatetimeStatusChangeLog Entry
02024-05-29 15:26:05ID requested
12025-04-25 12:56:00announced
Publication List
10.1101/2024.06.23.600279;
Dahabieh MS, DeCamp LM, Oswald BM, Kitchen-Goosen SM, Fu Z, Vos M, Compton SE, Longo J, Williams KS, Ellis AE, Johnson A, Sodiya I, Vincent M, Lee H, Sheldon RD, Krawczyk CM, Yao C, Wu T, Jones RG, NRF2-dependent regulation of the prostacyclin receptor PTGIR drives CD8 T cell exhaustion. bioRxiv, ():(2024) [pubmed]
Keyword List
submitter keyword: adoptive cell therapy,T cell exhaustion, immune checkpoint
Contact List
Russell Jones
contact affiliationMetabolism and Nutritional Program Van Andel Institute
contact emailrussell.jones@vai.org
lab head
Hyoungjoo Lee
contact affiliationVan Andel Institute
contact emailhyoungjoo.lee@vai.org
dataset submitter
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Dataset FTP location
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