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A Private Crosstalk Established by Tumor-Targeted Cytokine Release Rescues CAR-T Activity and Engages Host T Cells against Glioblastoma

GSE259346 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/07/01 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 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
Mus musculus (mouse)
Samples
12 samples: 3 × GBM mouse treated with Empty LV vs 3 × GBM mouse treated with oIL2 vs 3 × GBM mouse treated with IFN+oIL2 vs 3 × GBM mouse treated with IFNGroups 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)
Chimeric antigen receptor T cells (CAR-Ts) have shown limited efficacy in solid tumors, due to poor penetration, constrained activity, and early exhaustion into the immunosuppressive tumor microenvironment (TME). While cytokines can counteract immune-suppression, their systemic administration entails risk of toxicities and counter-regulatory responses.
Read the full summary ↓
Here, we leveraged on a population of tumor associated TIE2 expressing macrophages (TEMs) to release IFN- and/or orthogonal IL-2 (oIL2) at the tumor site. TEM-mediated cytokine delivery rescued CAR-Ts functionality against the clinically relevant antigen B7-H3 in an immunocompetent mouse model of glioblastoma multiforme (GBM) which was refractory to anti-B7-H3 CAR-Ts alone. Immunophenotypic and transcriptomic analyses showed that TEM-mediated cytokine delivery counteracted premature CAR-Ts terminal exhaustion and sustained their effector/memory state which accounts for tumor cell elimination. This was mirrored by delayed tumor growth and prolonged mice survival achieving a synergistic effect in the IFN- + oIL2 group receiving CAR-Ts. Importantly, IFN-, especially when combined with oIL2, also triggered an endogenous T cell response against tumor associated antigens other than B7-H3. Altogether our findings suggest that the combination approach between the two genes and cell therapy strategies presented here, and already under clinical testing as monotherapies, could achieve synergistic therapeutic effect also in GBM patients.
This dataset
Open GSE259346 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 GSE259346_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 PRJNA1081289 and SRA study SRP492001. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
3 × GBM mouse treated with Empty LV vs 3 × GBM mouse treated with oIL2 vs 3 × GBM mouse treated with IFN+oIL2 vs 3 × GBM mouse treated with IFN

Supports a between-group comparison across 12 samples.

How we read this: 4 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
Datasets on a similar topic

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.