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Unleashing natural IL-18 activity using an anti-IL-18BP blocker antibody induces potent immune stimulation and anti-tumor effects

GSE239473 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2024/03/15 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: 12 samples, each with a distinct title — no replicated groupsGroups 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
Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor EffectsCancer immunology research · 2024
Summary (written by the submitters)
Recombinant cytokines have limited anti-cancer efficacy mostly due to narrow therapeutic window and systemic adverse effects. IL-18 is an inflammasome induced proinflammatory cytokine that enhances T and NK cell activity and stimulates IFNg production. The activity of IL-18 is naturally blocked by a high affinity endogenous binding protein (IL-18BP).
Read the full summary ↓
IL-18BP is induced in the tumor microenvironment (TME) in response to IFNg upregulation in a negative feedback mechanism. In this study we found that IL-18 is upregulated in the TME compared to the periphery across multiple human tumors and most of it is bound to IL-18BP. Bound IL-18 levels were largely above the amount required for T cell activation in vitro, implying that releasing IL-18 in the TME could lead to potent T cell immune activation. To restore the activity of endogenous IL-18 we generated COM503, a high affinity anti-IL-18BP antibody (Ab), that blocks the IL-18BP:IL-18 interaction and displaces pre-complexed IL-18 to enhance T cell and NK cell activation. In vivo, administration of a surrogate anti-IL-18BP Ab, either alone or in combination with anti-PD-L1 Ab, resulted in significant tumor growth inhibition and increased survival across multiple mouse tumor models. Moreover, anti-IL-18BP Ab induced pronounced TME-localized immune modulation including an increase in polyfunctional non-exhausted T and NK cell numbers and activation. In contrast, no increase in inflammatory cytokines and lymphocyte numbers or activation state was observed in serum and spleen. Taken together, blocking IL-18BP using an Ab is a promising novel approach to harness cytokine biology for the treatment of cancer.
Published in
Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor Effects
Menachem A, Alteber Z, Cojocaru G et al. · Cancer immunology research 2024 · PMID 38592331 · doi:10.1158/2326-6066.CIR-23-0706
This dataset
Open GSE239473 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 GSE239473_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 PRJNA999351 and SRA study SRP451835. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38592331) ↗
Study design
12 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 12 sample titles: 12 distinct titles with little repetition. 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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