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Inhibiting CXCR4 Attenuates TOX-Programmed Exhausted Phenotype of CD8+ T cells via Regulating JAK2/STAT3 Pathway [ChIP-Seq]

GSE255177 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 20 samples Submitted 2025/01/28 Platform GPL24676Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 20 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Samples
20 samples: 8 conditions, mostly in duplicateGroups 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.
Paper
CXCR4 orchestrates the TOX-programmed exhausted phenotype of CD8(+) T cells via JAK2/STAT3 pathwayCell genomics · 2024
Summary (written by the submitters)
T-cell exhaustion (Tex) phenotype has limited the efficacy of single-agent immune checkpoint blockade (ICB) in cancer immunotherapy, underscoring the need to target upstream pathways. Clinical trials have indicated that CXCR4 antagonists enhance anti-cancer activity. However, the specific mechanisms through which CXCR4 contributes to immune cell phenotypes are not fully understood.
Read the full summary ↓
By targeting CXCR4 using antagonists or transgenic mice (Cxcr4flox/flox LckCre), we effectively attenuated the Tex phenotype and enhanced the functional T-cell phenotype in vivo. Additionally, single-cell RNA/TCR-seq analyses demonstrated that CXCR4 inhibition promotes anti-PD-1 immunotherapy by reducing CD8+ Tex phenotype and enriching the abundance of TCR clonotypes in vivo. Mechanically, we found that CXCR4-blocking T cells mitigate Tex phenotype by regulating the JAK2-STAT3 pathway, reducing the interaction between p-STAT3 and TOX. Single-cell ATAC/RNA-seq validated that CXCR4 deficiency epigenetically orchestrates the transition from functional to exhausted phenotypes in CD8+ T cells. Altogether, we demonstrate a mechanism of targeting CXCR4 to orchestrate CD8+ Tex cells in cancers and provide a rationale for the combined CXCR4 antagonists and ICBs in clinical trials.
Published in
CXCR4 orchestrates the TOX-programmed exhausted phenotype of CD8(+) T cells via JAK2/STAT3 pathway
Cao C, Xu M, Wei Y et al. · Cell genomics 2024 · PMID 39317187 · doi:10.1016/j.xgen.2024.100659
This dataset
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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 GSE255177_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1073900 and SRA study SRP488478. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39317187) ↗
Study design
8 conditions, mostly in duplicate
Jurkat_control_tox ×2 Jurkat_plerixafor_tox ×2 Jurkat_control_pstat3 ×2 Jurkat_plerixafor_pstat3 ×2 Mouse T cell_control_tox ×2 Mouse T cell_plerixafor_tox ×2 Mouse T cell_control_pstat3 ×2 Mouse T cell_plerixafor_pstat3 ×2 +4 more

Supports a between-group comparison across 16 samples.

How we read this: 8 replicated groups read from 20 sample titles; they account for 16 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
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