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JNK knockdown enhances CAR-T cell cytotoxicity through NFATc1 in preclinical models of ovarian cancer

GSE308299 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/11/18 Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 12 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)
Topic
Ovarian cancerThis series is part of our curated briefing on it.
Samples
12 samples: 6 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
JNK knockdown enhances CAR-T cell cytotoxicity through elevated NFATc1-dependent transcription in preclinical ovarian cancer modelsJournal for immunotherapy of cancer · 2025
Summary (written by the submitters)
Background: Boosting the performance of chimeric antigen receptor T (CAR-T) cell therapy in solid tumors may provide a substantial advantage for cancer patients. Recognizing the vital role of the nuclear factor of activated T cells (NFAT) in T cell function, we hypothesized the strategic regulation of NFAT activity by targeting c-Jun N-terminal Kinases (JNK) can bolster the tumor-eradicating potential of CAR-T cells.
Read the full summary ↓
Methods: We developed a lentivirally encoded short-hairpin RNA (shRNA) for stable knockdown of JNK in CAR-T cells. CAR-T cells targeting human epidermal growth factor receptor 2 (HER2) were produced from human peripheral blood. Functionality was tested in vitro and in two xenograft models of human ovarian cancer. Results: JNK knockdown in CAR-T cells suppressed antigen-induced stimulation and helper T cell cytokine production, while enhancing anti-tumor cytotoxicity in vitro and in ovarian cancer xenograft experiments. Mechanistically, JNK knockdown altered NFAT signaling to facilitate NFATc1-dependent transcription, leading to elevated levels of granzyme B expression. Conclusions: JNK signaling is a significant regulator of CAR-T cell cytotoxicity, offering a potential strategy to directly enhance CAR-T effectiveness in human cancer therapies.
Published in
JNK knockdown enhances CAR-T cell cytotoxicity through elevated NFATc1-dependent transcription in preclinical ovarian cancer models
Kuhlmann CJ, Jepson CE, Blucas MT et al. · Journal for immunotherapy of cancer 2025 · PMID 41253493 · doi:10.1136/jitc-2025-012968
This dataset
Open GSE308299 in finder → Find more human RNA-seq datasets → Ovarian cancer landscape →
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 GSE308299_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 PRJNA1330158 and SRA study SRP621026. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41253493) ↗
Study design
6 conditions, mostly in duplicate
shScramble_donor1 ×2 shScramble_donor2 ×2 shScramble_donor3 ×2 shJNK_donor1 ×2 shJNK_donor2 ×2 shJNK_donor3 ×2

Supports a between-group comparison across 12 samples.

How we read this: 6 replicated groups read from 12 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
More Ovarian cancer datasets

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