GEO series

Pan-cancer mapping of single CD8+ T cell profiles reveals a TCF1:CXCR6 axis regulating CD28 co-stimulation and anti-tumor immunity I

GSE234974 Mus musculus (mouse) Single-cell RNA-seq 24 samples Submitted 2024/07/02 Platform GPL19057

At a glance

Single-cell RNA-seq · mouse · 24 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: 24 samples: 6 conditions, mostly with about 4 replicates eachGroups 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)

Cytotoxic CD8+ T cells need to persist and function in diverse tumor microenvironments to exert their effects. Here, we developed Generalizable Matrix Decomposition Framework (GMDF), a matrix factorization algorithm that recovers both shared and tumor type-specific transcriptional programs from diverse data sets, and applied it to a scRNA-seq compendium of 38,852 CD8+ T cells from 141 patients spanning nine different human cancers.

Read the full summary ↓

Our meta-single-cell analyses uncovered a pan-cancer T cell dysfunction program that was predictive of clinical responses to checkpoint blockade in melanoma and highlighted CXCR6 as a pan-cancer marker of chronically activated T cells. CXCR6 transcription was activated by AP-1 factors and repressed by TCF1. In mouse models, CXCR6 expression increased with tumor progression and upon checkpoint blockade. CXCR6 deletion in CD8+ T cells increased apoptosis of PD1+Tim3+ cells and compromised tumor growth control due to suppressed expression of survival factors and CD28 co-stimulation, revealing a role for CXCR6 in opposing PD1-mediated suppression of CD28 signaling. Our application of GMDF led us to discover a TCF1:CXCR6 axis that counterbalances PD1-mediated suppression of CD8+ cell responses and is essential for effective anti-tumor immunity.

This dataset

Open GSE234974 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 GSE234974_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 PRJNA983823 and SRA study SRP443771. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

6 conditions, mostly with about 4 replicates each

cKO_Mouse1_TP ×4 cKO_Mouse2_TP ×4 cKO_Mouse3_TP ×4 WT_Mouse4_TP ×4 WT_Mouse5_TP ×4 WT_Mouse6_TP ×4

Supports a between-group comparison across 24 samples.

How we read this: 6 replicated groups read from 24 sample titles; they account for 24 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

GSM7487573 cKO_Mouse1_TP0 cKO_Mouse1_TP
GSM7487574 cKO_Mouse2_TP0 cKO_Mouse2_TP
GSM7487575 cKO_Mouse3_TP0 cKO_Mouse3_TP
GSM7487576 WT_Mouse4_TP0 WT_Mouse4_TP
GSM7487577 WT_Mouse5_TP0 WT_Mouse5_TP
GSM7487578 WT_Mouse6_TP0 WT_Mouse6_TP
GSM7487579 cKO_Mouse1_TP4 cKO_Mouse1_TP
GSM7487580 cKO_Mouse2_TP4 cKO_Mouse2_TP
GSM7487581 cKO_Mouse3_TP4 cKO_Mouse3_TP
GSM7487582 WT_Mouse4_TP4 WT_Mouse4_TP
GSM7487583 WT_Mouse5_TP4 WT_Mouse5_TP
GSM7487584 WT_Mouse6_TP4 WT_Mouse6_TP
GSM7487585 cKO_Mouse1_TP8 cKO_Mouse1_TP
GSM7487586 cKO_Mouse2_TP8 cKO_Mouse2_TP
GSM7487587 cKO_Mouse3_TP8 cKO_Mouse3_TP
GSM7487588 WT_Mouse4_TP8 WT_Mouse4_TP
GSM7487589 WT_Mouse5_TP8 WT_Mouse5_TP
GSM7487590 WT_Mouse6_TP8 WT_Mouse6_TP
GSM7487591 cKO_Mouse1_TP24 cKO_Mouse1_TP
GSM7487592 cKO_Mouse2_TP24 cKO_Mouse2_TP
GSM7487593 cKO_Mouse3_TP24 cKO_Mouse3_TP
GSM7487594 WT_Mouse4_TP24 WT_Mouse4_TP
GSM7487595 WT_Mouse5_TP24 WT_Mouse5_TP
GSM7487596 WT_Mouse6_TP24 WT_Mouse6_TP

Datasets on a similar topic

GSE306744 Pre-division TCF1 downregulation determines long-term effector and memory CD8 T cell fates [RNA-Seq] 31 samples shares tcf1, cd8
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GSE316541 α2,6-Sialoglycan-regulated anti-tumor immunity of tumor-infiltrating CD8+ T cells in the tumor microenvironment [CD8+T] 27 samples shares cd8, anti-tumor
GSE277610 Endothelial PD-L1 brakes CD8+ T cell exhaustion, empowering anti-tumor immunity in non-small cell lung cancer 17 samples shares cd8, anti-tumor
GSE207029 Blockade of avb8 integrin synergizes with checkpoint inhibition to enhance anti-tumor immunity through Cxcl9-dependent augmentation of CD8+ T cell cytotoxicity 12 samples shares cd8, anti-tumor
GSE316540 α2,6-Sialoglycan-regulated anti-tumor immunity of tumor-infiltrating CD8+ T cells in the tumor microenvironment 9 samples shares cd8, anti-tumor
GSE296763 Mitochondrial respiration is necessary for CD8 T cell proliferation and cell fate 99 samples shares cd8
GSE334845 Discovery of Tcf7 regulators with clonally-resolved CRISPR screens identifies Trim28 as a mediator of CD8 T cell differentiation in tumors [RNA-Seq] 86 samples shares cd8

Search all mouse RNA-seq datasets in GEO →

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