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Senescent cancer-associated fibroblasts in pancreatic adenocarcinoma suppress CD8+ T cell activation and inhibit response to immune checkpoint therapy [Cultured_Human_Mouse]

GSE235233 Homo sapiens (human) RNA-seq (gene expression) 16 samples Submitted 2024/06/06 Platform GPL17021Platform GPL16791
At a glance

RNA-seq (gene expression) · human · 16 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
16 samples: 5 × Cultured mouse CAFs_Non-sen vs 4 × Cultured human CAFs_Sen vs 4 × Cultured mouse CAFs_Sen vs 3 × Cultured human CAFs_Non-senGroups 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
Senescent cancer-associated fibroblasts in pancreatic adenocarcinoma restrict CD8(+) T cell activation and limit responsiveness to immunotherapy in miceNature communications · 2024
Summary (written by the submitters)
Senescent cells appear within tumors and their stroma, exerting complex pro- and anti-tumorigenic functions. The effects of senescent tumor stromal cells are mostly unknown, as is the potential for targeting such senescent cells for improved therapy. Here we uncover the presence of a senescent subset of cancer-associated fibroblasts (CAFs) within pancreatic adenocarcinomas and in premalignant pancreatic lesions.
Read the full summary ↓
Senescent CAFs show reduced proliferation, and are often associated with the inflammatory CAF (iCAF) subtype. We isolated and characterized senescent CAFs from mouse models and directly from human patients, and found that they express elevated levels of immune-regulatory genes. In a panel of mouse PDACs, high levels of senescent CAFs correlated with low T cell infiltration. Removal of senescent CAFs from PDAC stroma, either genetically or through treatment with the senolytic drug ABT-199 (venetoclax), a Bcl2 inhibitor, increased rates of activated cytotoxic CD8+ T cells within tumors. Conversely, activation of CAF senescence within PDACs led to reduced CD8+ T cell numbers. Media from senescent PDAC CAFs inhibited T cell proliferation and activation. We show that implanted PDAC tumors show improved response to immune checkpoint therapy when co-treated with the senolytic drug. These results reveal that the presence of senescent CAFs in PDAC stroma acts to repress cytotoxic T cell activity, and suggest that their targeted elimination through senolytic treatment may enhance immunotherapy.
Published in
Senescent cancer-associated fibroblasts in pancreatic adenocarcinoma restrict CD8(+) T cell activation and limit responsiveness to immunotherapy in mice
Assouline B, Kahn R, Hodali L et al. · Nature communications 2024 · PMID 39039076 · doi:10.1038/s41467-024-50441-7
This dataset
Open GSE235233 in finder → Find more 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 GSE235233_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 PRJNA985609 and SRA study SRP444838. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39039076) ↗
Study design
5 × Cultured mouse CAFs_Non-sen vs 4 × Cultured human CAFs_Sen vs 4 × Cultured mouse CAFs_Sen vs 3 × Cultured human CAFs_Non-sen

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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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