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Immune-related cutaneous adverse events display distinct clinical and molecular characteristics, depending on immune checkpoints targeted

GSE297863 Homo sapiens (human) RNA-seq (gene expression) 32 samples Submitted 2025/06/25 Platform GPL24676Platform GPL16791
At a glance

RNA-seq (gene expression) · human · 32 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
Homo sapiens (human)
Samples
32 samples: 5 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
Immune-Related Cutaneous Adverse Events Display Distinct Clinical and Molecular Characteristics, Depending on Immune Checkpoints TargetedCancers · 2025
Summary (written by the submitters)
Background/Objectives: Immune-related cutaneous adverse events (ircAE) are common complications of cancer immunotherapy and provide insight into immune-related ad-verse events (irAE) more broadly. To enhance our molecular understanding, we char-acterized ircAE resulting from single-agent (PD1) and combined immunotherapy reg-imens (P+C).
Read the full summary ↓
Clinically, maculopapular rashes (MPR) and toxic epidermal necrolysis (TEN) resemble ircAE, providing a valuable basis for investigations. Methods: To in-vestigate the transcriptome and immune infiltrates in ircAE, we conducted transcriptomic analyses and multiplexed immunohistochemistry on skin biopsies from patients re-ceiving PD1 and P+C, as well as those with MPR, TEN, and healthy controls. Results: Principal component analysis revealed distinct transcriptomic clustering between ircAE, MPR, and TEN. Specifically, PD1 ircAE exhibited a gene expression profile similar to TEN, with upregulation of Type-I-response-related genes (e.g., CXCL9 Log2FC 5.34, p<0.0001, CXCL10 Log2FC 6.03, p<0.0001), while P+C ircAE more closely resembled MPR. Immune infiltrates differed significantly between all groups (p=0.002 by PER-MANOVA for all groups). CD4 T-cells were abundant in the dermis of ircAE from any type of immunotherapy. However, PD1 stained positive in 1.07% of CD4 cells with PD1 monotherapy, compared to 0.3%, 0.4%, and 0.08% in P+C, MPR, and TEN, respectively. Conclusions: This study identified distinct molecular and cellular signatures in ircAE depending on the type of immune checkpoint blockade. aPD1-associated ircAE share similarities with the cytotoxic profile of TEN, while P+C more closely mirrored MPR. These findings support the need for tailored management strategies for ircAE, emphasizing personalized therapeutic approaches to minimize treatment interruptions while preserving the efficacy of cancer immunotherapy.
Published in
Immune-Related Cutaneous Adverse Events Display Distinct Clinical and Molecular Characteristics, Depending on Immune Checkpoints Targeted
Kraehenbuehl L, Winkelbeiner N, Turko P et al. · Cancers 2025 · PMID 40563643 · doi:10.3390/cancers17121992
This dataset
Open GSE297863 in finder → Find more human 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 GSE297863_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 PRJNA1266619 and SRA study SRP587013. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40563643) ↗
Study design
5 conditions, mostly in triplicate
Healthy_Skin, ×13 maculopapular drug rash ×7 ircAE PD1-Monotherapy ×6 toxic epidermal necrolysis ×3 ircAE combined CTLA4/PD1 ×3

Supports a between-group comparison across 32 samples.

How we read this: 5 replicated groups read from 32 sample titles; they account for 32 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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