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Coactivation of innate immune suppressive cells induces acquired resistance against cancer immunotherapy targeting the innate immune system [TIICs RNA-seq]

GSE281467 Mus musculus (mouse) RNA-seq (gene expression) 30 samples Submitted 2025/01/15 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 30 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
30 samples: 10 conditions, mostly in triplicateGroups 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
Coactivation of innate immune suppressive cells induces acquired resistance against combined TLR agonism and PD-1 blockadeScience translational medicine · 2025
Summary (written by the submitters)
Immune checkpoint blockade therapy has been successfully applied in clinical settings as a standard therapy for many cancer types, but its clinical efficacy is restricted to patients with immunologically hot tumors. Various strategies to modify the tumor microenvironment (TME), such as Toll-like receptor (TLR) agonists, have been explored but have not been successful.
Read the full summary ↓
Here, we identified a mechanism of acquired resistance to combination treatment consisting of an agonist for multiple TLRs, OK-432 (Picibanil), and PD-1 blockade. Adding the TLR agonist failed to convert the TME from immunogenically cold to hot. The combination treatment did not augment antitumor immunity, particularly CD8+ T cell responses, in multiple animal models. The failure was attributed to the coactivation of innate suppressive cells, such as CD11b+ Gr1+ Ly6C- Ly6G+ myeloid-derived suppressor cells (MDSCs) expressing CXCR2, through high CXCL1 production by macrophages in the TME upon OK-432 treatment. Thus, a triple combination treatment with OK-432, PD-1 blockade, and a CXCR2 neutralizing antibody overcame the resistance induced by MDSCs, resulting in a far stronger antitumor effect than that of any dual combination or single treatment. The accumulation of MDSCs was similarly observed in the pleural effusion of lung cancer patients after OK-432 administration. We propose that successful combination cancer immunotherapy stimulating innate immunity against immunologically cold tumors requires modulation of unwanted activation of innate immune suppressive cells, including MDSCs.
Published in
Coactivation of innate immune suppressive cells induces acquired resistance against combined TLR agonism and PD-1 blockade
Nishinakamura H, Shinya S, Irie T et al. · Science translational medicine 2025 · PMID 39937883 · doi:10.1126/scitranslmed.adk3160
This dataset
Open GSE281467 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 GSE281467_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 PRJNA1183892 and SRA study SRP544120. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39937883) ↗
Study design
10 conditions, mostly in triplicate
MC38 ×3 MC38OVA ×3 EMT6 ×3 LL2 ×3 CT26 ×3 CT26NYESO1 ×3 CMS5a ×3 Renca ×3 +2 more

Supports a between-group comparison across 30 samples.

How we read this: 10 replicated groups read from 30 sample titles; they account for 30 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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