PXD052688 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | The Prostacyclin Receptor is a NRF2-regulated Immune Checkpoint in CD8 T cells |
Description | Immune 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 |
HostingRepository | PRIDE |
AnnounceDate | 2025-04-25 |
AnnouncementXML | Submission_2025-04-25_12:55:59.811.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Hyoungjoo Lee |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | No PTMs are included in the dataset |
Instrument | Orbitrap Eclipse |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2024-05-29 15:26:05 | ID requested | |
⏵ 1 | 2025-04-25 12:56:00 | announced | |
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 affiliation | Metabolism and Nutritional Program Van Andel Institute |
contact email | russell.jones@vai.org |
lab head | |
Hyoungjoo Lee |
contact affiliation | Van Andel Institute |
contact email | hyoungjoo.lee@vai.org |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD052688
- Label: PRIDE project
- Name: The Prostacyclin Receptor is a NRF2-regulated Immune Checkpoint in CD8 T cells