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NR4a knock-down in HER2 CAR-T cells improves T cell longevity and promotes solid tumor eradication [RNA-Seq]

GSE241456 Homo sapiens (human) RNA-seq (gene expression) 14 samples Submitted 2024/08/28 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 14 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
14 samples: 3 × cont_pre vs 3 × KO_pre vs 3 × cont vs 3 × KOGroups 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
NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumorsJournal for immunotherapy of cancer · 2024
Summary (written by the submitters)
Chimeric antigen receptor (CAR)-T cell therapy targeting human CD19 have demonstrated clinical efficacy against B-cell malignancies. However, CAR-T cell therapy's efficacy against solid tumors is limited due to factors like low tumor-associated antigens, infiltration rate, and T cell exhaustion. We have shown that deleting NR4a genes in CAR-T cells prevents T cell exhaustion and improved their therapeutic effects on solid tumors in a mouse model.
Read the full summary ↓
To further explore this for human, we deleted all three NR4a family factors in CAR-T cells that recognize Epidermal Growth Factor Receptor type 2 (HER2) using the CRISPR/Cas9 system. These modified CAR-T cells (NR4a-TKO CAR-T) exhibited resistance to exhaustion, increased tumor-killing activity, and higher efficacy in tumor regression and survival rate in a human lung carcinoma model in mice. The enhanced therapeutic effects were associated with increased cytokine expression, reduced exhaustion-related gene expression, and improved persistence within tumors. We propose that targeting NR4a could be a promising strategy for developing superior CAR-T cells against solid tumors.
Published in
NR4A ablation improves mitochondrial fitness for long persistence in human CAR-T cells against solid tumors
Nakagawara K, Ando M, Srirat T et al. · Journal for immunotherapy of cancer 2024 · PMID 39151930 · doi:10.1136/jitc-2023-008665
This dataset
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.

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 GSE241456_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1008189 and SRA study SRP456529. Searching any of these in the dataset finder brings you back here.

Study design
3 × cont_pre vs 3 × KO_pre vs 3 × cont vs 3 × KO

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 14 sample titles; they account for 12 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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