GEO series

Extracellular vesicles from obese visceral adipose promote pancreatic cancer development and resistance to immune checkpoint blockade therapy [ATAC-seq]

GSE254919 Mus musculus Genome binding/occupancy profiling by high throughput sequencing 12 samples Submitted 2025/10/28 Platform GPL24247

Summary

Obesity is correlated with multitype of cancer development, and pancreatic ductal adenocarcinoma (PDAC) in obese patients often shows dismal prognosis and resistance to immune checkpoint blockade (ICB) therapy. The molecular mechanism for these phenomena is largely unknown. Here we show that obese visceral adipose tissues (VAT) can talk to distant PDAC by delivering their extracellular vesicle (EV) carrying signal molecules. We reveal that PDAC cells can take in VAT-EVs to their lysosomes where EVs-delivered Cathepsin A (Ctsa) stabilize ribonuclease Rnaset2b to produce extra pseudouridines from RNA cleavage. Pseudouridines released from cancer cells activate mast cells which inhibit CD8+ T cell activity, forming an immunosuppressive tumor microenvironment which enhances cancer progression and resistance to ICB. We also demonstrate the harmful effects of VAT-EV CTSA-pseudouridine-mast cell axis for PDAC in obese patients. Animal experiments indicate that Ctsa knockdown effectively enhances the ICB efficacy on PDAC. Our study uncovers a mechanism connecting obesity and cancer which holds promise for developing new therapeutic strategy for obesity related cancers.

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Direct links to NCBI, no account and no request form: the whole study as GSE254919_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 12 samples. Raw sequencing reads are also available from ENA.

Whole study · RAW.tar ↓ Series matrix ↓ All supplementary files ↗ Raw reads on ENA ↗

Also filed as BioProject PRJNA1072629 and SRA study SRP487767. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

6 conditions, mostly in duplicate

MC9-cell_Vehicle_ATAC-Seq ×2 MC9-cell_PseudoU_ATAC-Seq ×2 KPC-cell_Vehicle_ATAC-Seq ×2 KPC-cell_PseudoU_ATAC-Seq ×2 CD8T-cell_Vehicle_ATAC-Seq ×2 CD8T-cell_PseudoU_ATAC-Seq ×2

Supports a between-group comparison across 12 samples.

6 replicated groups read from 12 sample titles; they account for 12 of them. Check it against the sample list below before relying on it.

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