GEO series

Complex I Inhibition combined with TLR Activation in the Breast Tumor Microenvironment Educates Cytotoxic Neutrophils [bulk RNA-seq]

GSE272921 Mus musculus (mouse) Single-cell RNA-seq 31 samples Submitted 2025/06/04 Platform GPL19057

At a glance

Single-cell RNA-seq · mouse · 31 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Mus musculus (mouse)
Samples: 31 samples
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: Complex I inhibition combined with TLR activation in the breast tumor microenvironment educates cytotoxic neutrophilsScience advances · 2025

Summary (written by the submitters)

Neutrophils have emerged as diverse regulators of tissue states, displaying functions in both the resolution and promotion of tissue inflammation. While neutrophils have widely been associated with tumor promotion, immune suppression, and poor patient outcome, we provide evidence to support direct tumor cytotoxic properties of neutrophils.

Read the full summary ↓

Using various models of murine breast cancer; we establish that TLR-mediated engagement, combined with complex I inhibition, within the breast tumor microenvironment, acting either directly or indirectly on neutrophils, primes these innate immune cells to acquire direct tumor killing properties, both in vitro and in vivo, and independently of CD8+ T cell immunity. TLR engagement stimulates emergency granulopoiesis, increasing levels of neutrophils in the circulation and infiltrating into tumors without inducing the formation of a pro-metastatic niche. Mechanistically, we show that systemic administration of various TLR agonists, while increasing systemic inflammation, elevates NFkB signalling in neutrophils, to contribute to their tumoricidal functions. Moreover, using bulk- and single-cell RNA sequencing, along with proteomics approaches, neutrophils that are trained to acquire these anti-tumorigenic functions, acquire enhanced secretory granule production and increased expression NADPH-oxidase machinery. Concomitantly, these tumoricidal neutrophils increase production of toxic levels of reactive oxygen species, which can be overcome with myeloperoxidase inhibitors or overexpression of ROS scavengers. Taken together, we describe a new class of neutrophils that possess direct and intrinsic tumoricidal functions, which can be exploited to eradicate immune cold breast tumors which otherwise are refractory to standard immunotherapies, including immune checkpoint blockade.

Published in

Complex I inhibition combined with TLR activation in the breast tumor microenvironment educates cytotoxic neutrophils

Heath J, Ahn R, Sabourin V et al. · Science advances 2025 · PMID 40644540 · doi:10.1126/sciadv.adu5915

This dataset

Open GSE272921 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 GSE272921_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1139250 and SRA study SRP521794. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40644540) ↗

Samples in this study

The sample list for this study is not cached yet. Press Load samples and it will be fetched from NCBI.

+ 31 more — browse all 31 samples with per-sample file links →

Datasets on a similar topic

GSE272923 Complex I Inhibition combined with TLR Activation in the Breast Tumor Microenvironment Educates Cytotoxic Neutrophils. 35 samples shares tlr, microenvironment, neutrophils, inhibition, activation, cytotoxic, combined, educates
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GSE322775 Coordinated immune activation following KRAS inhibition reveals molecular pathways that potentiate and limit anti-tumor immunity 47 samples shares inhibition, activation
GSE248058 Stroma reprogramming by FAK synergizes with MAPK inhibition and renders PDAC responsive to cytotoxic- and immuno-therapies II 18 samples shares inhibition, cytotoxic
GSE317949 Rational design of immune gene therapy combinations via in vivo CRISPR activation screening of tumor microenvironment modulators [APCM_BulkRNASeq_OT1] 15 samples shares microenvironment, activation

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