Project 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

2025-04-25 | PXD052688 | Pride

E-MTAB-3578

Project description:RNA-Seq CAGE (Cap Analysis of Gene Expression) analysis of mice cells in RIKEN FANTOM5 project

2015-06-04 | E-MTAB-3578 | ExpressionAtlas

E-GEOD-50554

Project description:RNA-Seq analysis of KLF3 knockout E14.5 TER119+ (erythroid) murine fetal liver cells

2019-05-14 | E-GEOD-50554 | ExpressionAtlas

E-GEOD-59831

Project description:Transcriptome analysis of isolated stormal cells and tumor epithelial cells in mouse lung cancer by RNA-Seq

2019-05-14 | E-GEOD-59831 | ExpressionAtlas

E-GEOD-97324

Project description:RNA-seq analysis of MCT8-deficient and healthy control brain microvascular endothelial cells (BMECs) and neural cells