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Antigen experience history directs distinct functional states of CD8+ CAR T cells during the anti-leukemia response

GSE281486 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2024/11/14 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 24 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
24 samples: 8 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.
Paper
Antigen experience history directs distinct functional states of CD8(+) CAR T cells during the antileukemia responseNature immunology · 2025
Summary (written by the submitters)
Adoptive transfer of immune cells expressing chimeric antigen receptors (CARs) is an effective therapy for B-lineage malignancies. However, most patients will relapse and this therapeutic has yet to show strong efficacy in other hematologic or solid tumors. One opportunity for improvement lies in the ability to select or generate T cells that have the highest potential for potent anti-tumor responses and T cell persistence.
Read the full summary ↓
Here, we dissect the biology of CD8+ CAR T cells by controlling whether the T cell has encountered cognate TCR antigen prior to CAR generation. We find that prior antigen experience influences multiple aspects of in vitro and in vivo CAR T cell functionality, boosting effector function and leukemia clearance in the setting of limiting target antigen density. However, this comes at the expense of proliferative capacity, resistance to dysfunction, and clearance of wildtype leukemia in the setting of limiting CAR+ cell dose. Epigenetic and transcriptomic comparisons of these cell populations uncover that modulation of the Runx2 transcription factor differentially impacts CAR T cell functionality depending on prior cell state. Collectively, our data demonstrate that prior antigen experience status determines functional attributes of a CAR T cell, as well as amenability to functional enhancement by transcription factor modulation.
Published in
Antigen experience history directs distinct functional states of CD8(+) CAR T cells during the antileukemia response
DeGolier KR, Danis E, D'Antonio M et al. · Nature immunology 2025 · PMID 39747430 · doi:10.1038/s41590-024-02034-1
This dataset
Open GSE281486 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 GSE281486_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1184132 and SRA study SRP544213. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39747430) ↗
Study design
8 conditions, mostly in triplicate
RUNX2, Memory, PostCAR, Exp1, T ×3 Memory, PostCAR, Exp1, T ×3 RUNX2, Naïve, PostCAR, Exp1, T ×3 Naïve, PostCAR, Exp1, T ×3 RUNX2, Memory, PostCAR, Exp2, T ×3 Memory, PostCAR, Exp2, T ×3 RUNX2, Naïve, PostCAR, Exp2, T ×3 Naïve, PostCAR, Exp2, T ×3

Supports a between-group comparison across 24 samples.

How we read this: 8 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
Datasets on a similar topic

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