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Tumor-site directed A1R expression enhances CAR T cell function and improves efficacy against solid tumors. [CD8 inducible human RNAseq]

GSE284619 Homo sapiens (human) RNA-seq (gene expression) 36 samples Submitted 2025/03/16 Platform GPL18573
At a glance

RNA-seq (gene expression) · human · 36 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
Homo sapiens (human)
Samples
36 samples: 12 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
Tumor site-directed A1R expression enhances CAR T cell function and improves efficacy against solid tumorsNature communications · 2025
Summary (written by the submitters)
The efficacy of Chimeric Antigen Receptor (CAR) T cells against solid tumors is limited by immunosuppressive factors in the tumor microenvironment (TME) including adenosine, which suppresses CAR T cells through activation of the A2A receptor (A2AR). To overcome this, CAR T cells were engineered to express A1 receptor (A1R), a receptor that signals inversely to A2AR.
Read the full summary ↓
Using murine and human CAR T cells, constitutive A1R overexpression was demonstrated to significantly enhance CAR T cell effector function albeit at the expense of CAR T cell persistence. Through a novel CRISPR/Cas9 “knock-in” approach we demonstrated that CAR T cells engineered to express A1R in a tumor-localized manner, led to enhanced anti-tumor efficacy dependent on the transcription factor IRF8 and was transcriptionally unique when compared to A2AR deletion. This data provides a novel approach for enhancing CAR T cell efficacy in solid tumors and provides proof of principle for site-directed expression of factors that promote effector T cell differentiation.
Published in
Tumor site-directed A1R expression enhances CAR T cell function and improves efficacy against solid tumors
Sek K, Chen AXY, Cole T et al. · Nature communications 2025 · PMID 40610421 · doi:10.1038/s41467-025-59021-9
This dataset
Open GSE284619 in finder → Find more human 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 GSE284619_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 PRJNA1199945 and SRA study SRP552302. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40610421) ↗
Study design
12 conditions, mostly in triplicate
Control CAR T cells- unstimulated ×3 Control CAR T cells- Tumor Stimulated stim 1 ×3 Control CAR T cells- Tumor Stimulated stim 2 ×3 Control CAR T cells- Tumor Stimulated stim 3 ×3 NR4A2/A1R CAR T cells- unstimulated ×3 NR4A2/A1R CAR T cells- Tumor Stimulated stim 1 ×3 NR4A2/A1R CAR T cells- Tumor Stimulated stim 2 ×3 NR4A2/A1R CAR T cells- Tumor Stimulated stim 3 ×3 +4 more

Supports a between-group comparison across 36 samples.

How we read this: 12 replicated groups read from 36 sample titles; they account for 36 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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