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Prostaglandin E2-EP2/EP4 signaling induces the tumor-infiltrating Treg phenotype for tumor growth

GSE282089 Mus musculus (mouse) Single-cell RNA-seq 20 samples Submitted 2025/11/24 Platform GPL21273Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 20 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Mus musculus (mouse)
Samples: 20 samples: 6 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

Foxp3+ regulatory T cells (Tregs) heavily infiltrate malignant tumors and restrict anti-tumor immunity. These tumor-infiltrating Tregs (TI-Tregs) adopt a distinct phenotype by expressing a unique set of genes including those encoding various co-stimulatory and co-inhibitory molecules. This TI-Treg gene expression signature is conserved in TI-Tregs across species and the types and stages of tumors, suggesting the presence of a common inducing mechanism or mechanisms in tumor microenvironment (TME).

Read the full summary ↓

However, identity of such a mechanism remains elusive. Here, we show that prostaglandin E2 (PGE2) produced in TME directly acts on its receptor EP2/EP4 on Tregs to induce the TI-Treg phenotype. Indeed, PGE2 added to TCR-activated Tregs induces a set of genes, many of which are included in the reported TI-Treg signature genes, in both induced Tregs (iTregs) and naturally occurring Tregs (nTregs), in a manner dependent on EP2 and EP4 via cAMP-PKA pathway. This is not limited to phenotypic changes, as EP4 agonist-treated Tregs exhibit potent suppressive activity to CD8+ T cells and strongly inhibit their proliferation and survival. Consistently, selective loss of EP2 and EP4 in mouse Tregs and pharmacological inhibition of EP2 and EP4 reduce expression of those genes in Tregs infiltrating LLC1 mouse syngeneic tumor, and significantly delay the tumor progression. In human FOXP3+iTregs, the expression of Treg signature genes, FOXP3, CD25 and CTLA4 as well as a typical TI-Treg signature gene, 4-1BB are significantly upregulated by PGE2-EP4 signaling. Furthermore, analysis of scRNA-seq of nasopharyngeal cancer patients demonstrates preferential expression of the TI-Treg signature genes in Tregs infiltrating the PTGShi tumor group compared to the PTGS2lo tumor group. These findings suggest that PGE2-EP2/EP4 signaling is one of the molecular mechanisms inducing the TI-Treg phenotype in TME.

This dataset

Open GSE282089 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE282089_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1187169 and SRA study SRP545662. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

6 conditions, mostly in triplicate

TITreg_Control ×4 TITreg_EP2EP4cKO ×4 nTreg_Vehicle ×3 nTreg_EP4ago ×3 Foxp3+iTreg_Vehicle ×3 Foxp3+iTreg_PGE2 ×3

Supports a between-group comparison across 20 samples.

How we read this: 6 replicated groups read from 20 sample titles; they account for 20 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8635741 nTreg_Vehicle_1 nTreg_Vehicle
GSM8635742 nTreg_Vehicle_2 nTreg_Vehicle
GSM8635743 nTreg_Vehicle_3 nTreg_Vehicle
GSM8635744 nTreg_EP4ago_1 nTreg_EP4ago
GSM8635745 nTreg_EP4ago_2 nTreg_EP4ago
GSM8635746 nTreg_EP4ago_3 nTreg_EP4ago
GSM8635747 TITreg_Control_1 TITreg_Control
GSM8635748 TITreg_Control_2 TITreg_Control
GSM8635749 TITreg_Control_3 TITreg_Control
GSM8635750 TITreg_Control_4 TITreg_Control
GSM8635751 TITreg_EP2EP4cKO_1 TITreg_EP2EP4cKO
GSM8635752 TITreg_EP2EP4cKO_2 TITreg_EP2EP4cKO
GSM8635753 TITreg_EP2EP4cKO_3 TITreg_EP2EP4cKO
GSM8635754 TITreg_EP2EP4cKO_4 TITreg_EP2EP4cKO
GSM8635755 Foxp3+iTreg_Vehicle_1 Foxp3+iTreg_Vehicle
GSM8635756 Foxp3+iTreg_Vehicle_2 Foxp3+iTreg_Vehicle
GSM8635757 Foxp3+iTreg_Vehicle_3 Foxp3+iTreg_Vehicle
GSM8635758 Foxp3+iTreg_PGE2_1 Foxp3+iTreg_PGE2
GSM8635759 Foxp3+iTreg_PGE2_2 Foxp3+iTreg_PGE2
GSM8635760 Foxp3+iTreg_PGE2_3 Foxp3+iTreg_PGE2

Datasets on a similar topic

GSE282087 Prostaglandin E2-EP2/EP4 signaling induces the tumor-infiltrating Treg phenotype for tumor growth [TITreg] 8 samples shares e2-ep2, ep4, tumor-infiltrating, prostaglandin, phenotype, induces, growth, treg
GSE282088 Prostaglandin E2-EP2/EP4 signaling induces the tumor-infiltrating Treg phenotype for tumor growth [iTreg] 6 samples shares e2-ep2, ep4, tumor-infiltrating, prostaglandin, phenotype, induces, growth, treg
GSE282086 Prostaglandin E2-EP2/EP4 signaling induces the tumor-infiltrating Treg phenotype for tumor growth [nTreg] 6 samples shares e2-ep2, ep4, tumor-infiltrating, prostaglandin, phenotype, induces, growth, treg
GSE242272 Prostaglandin E2-EP4 signaling shapes immunosuppressive tumor microenvironment in human tumors by suppressing bioenergetics and ribosome biogenesis in infiltrating immune cells [RNA-seq] 18 samples shares ep4, prostaglandin
GSE296033 Rebamipide Induces Hair Regeneration through EP4-Driven Lipid Metabolism Remodeling 6 samples shares ep4, induces
GSE294977 Transcriptomic profiling of tumor-infiltrating and lymph node-derived Treg and B cells in Foxp3-Cre-YFP and Foxp3-Cre-YFP Appl2f/f melanoma-bearing Mice 24 samples shares tumor-infiltrating, treg
GSE298145 Transcriptomic profiling of tumor-infiltrating Treg cells in Foxp3-Cre-YFP melanoma-bearing mice 7 samples shares tumor-infiltrating, treg
GSE311904 Protective Effects of Recombinant Depolymerase Dep44 Against K64-CRKP-Induced Pulmonary Infection in a Murine Infection Model 12 samples shares ep4

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