GEO series

PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors

GSE298396 Homo sapiens (human) RNA-seq (gene expression) 16 samples Submitted 2025/09/01 Platform GPL30173Platform GPL30172

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: 6 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: PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumorsProceedings of the National Academy of Sciences of the United States of America · 2025

Summary (written by the submitters)

Immunotherapy modalities have revolutionized cancer treatment for a number of metastatic and treatment-refractory tumor types. Still, many malignancies that are lacking in T cell infiltrates and immunologically “cold” fail to respond to these modalities. One approach to increase tumor immunogenicity has been to induce STING and downstream interferon signaling that is often dysregulated in “cold” tumors.

Read the full summary ↓

Despite some early success of STING agonists in preclinical cancer models, these approaches have not been successful in the clinic due to poor tumor penetrance and systemic toxicities. Here we performed a genome-wide CRISPR screen to uncover novel therapeutic targets to activate STING expression in human tumors. We identified Palmitoyl Protein Thioesterase1 (PPT1) as a negative regulator of STING highly expressed in “cold” ovarian and prostate tumors. Genetic or pharmacological PPT1 suppression increased STING protein stability and its downstream activation of interferon and inflammatory cytokine signaling to enhance T cell migration. Treatment of preclinical prostate and ovarian cancer models expressing low levels of STING with the small molecule PPT1 inhibitor GNS561 enhanced STING expression and activation, leading to infiltration and activation of cytotoxic T cells that turned these tumors “hot” and reduced tumor growth, fibrosis, and dissemination without toxicity. Further analysis demonstrated that PPT1 is associated with reduced STING expression, CD8+ T cell numbers, overall survival, and immunotherapy outcomes in ovarian and prostate cancer patients. Thus, PPT1 inhibition may be a promising approach to activate STING and potentiate the effects of immunotherapy in “cold” tumors.

Published in

PPT1 is a negative regulator of STING signaling in cancer cells and its inhibition reactivates immune surveillance in cold tumors

Chowdhury SR, Parikh CN, Kaur AN et al. · Proceedings of the National Academy of Sciences of the United States of America 2025 · PMID 40982692 · doi:10.1073/pnas.2514948122

This dataset

Open GSE298396 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 GSE298396_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 PRJNA1269077 and SRA study SRP588325. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40982692) ↗

Study design

6 conditions, mostly in triplicate

A1847_GNS5 ×3 PC3_GNS5 ×3 MYC_P53KO_DMSO ×3 MYC_P53KO_GNS5 ×3 A1847_DMSO ×2 PC3_DMSO ×2

Supports a between-group comparison across 16 samples.

How we read this: 6 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

GSM9013453 A1847_DMSO_R1 A1847_DMSO
GSM9013454 A1847_DMSO_R2 A1847_DMSO
GSM9013455 A1847_GNS5_R1 A1847_GNS5
GSM9013456 A1847_GNS5_R2 A1847_GNS5
GSM9013457 A1847_GNS5_R3 A1847_GNS5
GSM9013458 PC3_DMSO_R1 PC3_DMSO
GSM9013459 PC3_DMSO_R2 PC3_DMSO
GSM9013460 PC3_GNS5_R1 PC3_GNS5
GSM9013461 PC3_GNS5_R2 PC3_GNS5
GSM9013462 PC3_GNS5_R3 PC3_GNS5
GSM9013463 MYC_P53KO_DMSO_R1 MYC_P53KO_DMSO
GSM9013464 MYC_P53KO_DMSO_R2 MYC_P53KO_DMSO
GSM9013465 MYC_P53KO_DMSO_R3 MYC_P53KO_DMSO
GSM9013466 MYC_P53KO_GNS5_R1 MYC_P53KO_GNS5
GSM9013467 MYC_P53KO_GNS5_R2 MYC_P53KO_GNS5
GSM9013468 MYC_P53KO_GNS5_R3 MYC_P53KO_GNS5

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.