PXD052688

PXD052688 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2024-05-29 15:26:05	ID requested
⏵ 1	2025-04-25 12:56:00	announced

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]

submitter keyword: adoptive cell therapy,T cell exhaustion, immune checkpoint

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

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/2025/04/PXD052688

PRIDE project URI

• PRIDE
  1. PXD052688
     1. Label: PRIDE project
     2. Name: The Prostacyclin Receptor is a NRF2-regulated Immune Checkpoint in CD8 T cells