GEO series

Rebound Polarization of Monocyte-derived Tumor Macrophages Under Repeated Anti-CD40 Immunotherapy

GSE290320 Mus musculus (mouse) Single-cell RNA-seq 3 samples Submitted 2025/10/10 Platform GPL34290

At a glance

Single-cell RNA-seq · mouse · 3 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: 3 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: Stress-NRF2 response axis polarizes tumor macrophages and undermines immunotherapyJournal for immunotherapy of cancer · 2025

Summary (written by the submitters)

To investigate TAM phenotypes and potential stress-induced feedback mechanism upon immunotherapy, we treated MC38 tumor-bearing C57BL/6 mice with a single dose of agonistic anti-CD40 or isotype control on day 11 (1× anti-CD40) or with repeated doses on days  11,  13, and  15 (3× anti-CD40). Twenty-four hours after the last injection, tumors were harvested for flow cytometry and single-cell RNA sequencing (scRNA-seq).

Read the full summary ↓

A single anti-CD40 injection significantly elevated CD45+F4/80+ macrophage numbers. PCA on CD45+F4/80+ cell RNAseq data , followed by gene set enrichment analysis (GSEA) and transcription factor enrichment, revealed a pronounced transcriptional transformation. After the first round of immunotherapy, most macrophages shifted toward an IFN–STAT1–driven, immune-activated phenotype—reflecting a robust antitumor response. However, repeated anti-CD40 doses induced a rebound in macrophage gene expression, reverting toward the original “tumor-conditioned” state highlighted by strong Spp1 expression. This rebound raised questions about stress signals in the local tumor environment driving macrophage immunosuppression. Across all conditions, we detected a striking polarity along a phenotype gradient from Spp1+ immunocompromised TAMs towards immune-activated Cxcl9+ Cxcl10+ MHC class II macrophages.

Published in

Stress-NRF2 response axis polarizes tumor macrophages and undermines immunotherapy

Schaer DJ, Schulthess-Lutz N, Baselgia L et al. · Journal for immunotherapy of cancer 2025 · PMID 41176316 · doi:10.1136/jitc-2025-013063

This dataset

Open GSE290320 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 GSE290320_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 PRJNA1227479 and SRA study SRP565928. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41176316) ↗

Samples in this study

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

+ 3 more — browse all 3 samples with per-sample file links →

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