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Induced loss of TREX1 in host cells inflames the tumor micromilieu and invigorates CTL-mediated cancer control

GSE290383 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/05/04 Platform GPL34328
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: 6 × Tumor, Ctrl vs 6 × Tumor, iKOGroups 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)
Activation of local innate immunity in tumor tissue, aiming at induction of adaptive responses, is a major concept in cancer immunotherapy. The cGAS/STING pathway triggers type I IFN and pro-inflammatory cytokine responses upon detection of cytosolic DNA and can robustly enhance anti-tumor immunity. The DNase 3’ repair exonuclease 1 (TREX1) is a central component of cellular DNA disposal preventing accumulation of endogenous DNA in the cytosol, activation of cGAS and cell-intrinsic innate immune responses.
Read the full summary ↓
While constitutive TREX1-deficiency causes severe mendelian autoimmunity, temporary pharmacological inhibition of the enzyme may represent an efficient means to activate anti-tumor immunity. Induced inactivation of the Trex1 gene in mice (TREX1 iKO) resulted in improved immune control of established syngeneic tumors that was type I IFN- and CD8+ T cell-dependent. This was associated with a dramatic increase of immune cell infiltration of tumor tissue while other (non-tumor) tissues were not or marginally affected. TREX1 iKO triggered an inflammatory switch of intra-tumoral monocyte, macrophage and dendritic cell populations, associated with enhanced antigen presentation capacity. Invigoration of CD8 T cell responses was reflected in robust increase in cells differentiating along the exhaustion trajectory but expressing significant signatures of effector function. Combination of TREX1 iKO with immune checkpoint inhibition synergistically promoted tumor control. In addition to improved anti-tumor immunity upon loss of TREX1 in host cells, we also show that cancer cell-specific TREX1 deficiency synergizes with irradiation and checkpoint inhibition to enable tumor rejection and formation of long-term memory. We conclude that pharmacological TREX1 inhibition is a promising therapeutic approach to boost anti-tumor immunity.
This dataset
Open GSE290383 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 GSE290383_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 PRJNA1227743 and SRA study SRP566097. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
6 × Tumor, Ctrl vs 6 × Tumor, iKO

Supports a between-group comparison across 12 samples.

How we read this: 2 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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