GEO series

Trabectedin and olaparib combination primes cellular immunotherapy with HLA-independent killer lymphocytes against sarcoma preclinical models through the cGAS-STING pathway

GSE239639 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2025/05/05 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 24 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: 24 samples: 12 conditions, mostly in duplicateGroups 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: The cGAS-STING pathway is a master regulator of OCT4 expression in persistent sarcoma cells and enhances cellular immunotherapy with NK and CIK lymphocytesCancer immunology, immunotherapy : CII · 2025

Summary (written by the submitters)

Background. Advanced sarcomas have a severe prognosis, limited therapeutic options, and are seldom sensitive to immunotherapy with checkpoint inhibitors. Novel strategies are urgently needed. Methods. We set up a preclinical approach for testing the combination of chemotherapy (trabectedin) and PARP1 inhibitor (olaparib) to potentiate the HLA-independent cellular immunotherapy with natural killer (NK) or cytokine-induced killer (CIK) lymphocytes.

Read the full summary ↓

The NK/CIK activators NKG2DLs were studied by qRT-PCR and flow cytometry. Drug-induced transcriptomic events were studied by RNA sequencing and the activation of the cytosolic DNA sensing pathway (cGAS-STING-IRF3-IFNβ) was explored. Focusing on the putative cancer stem cell (CSCs) subpopulation, OCT4 marker was evaluated. IRF3 silencing experiments were done to investigate the role of the cGAS-STING pathway in the control of NKG2DLs. NK/CIK killing activity on both bulk and OCT4-positive cells was tested by viability assay and flow cytometry, respectively. Results. We obtained the enhancement of NK/CIK activity against sarcoma cell lines through an integrated approach based on the combination of trabectedin and olaparib. These drugs upregulated the NKG2DL expression at both mRNA and protein level by inducing the genotoxicity pathway (WP4286) and repressing the cellular response to DNA damage stimulus (GO:0006974). The drug treatment significantly increased the cytosolic DNA content and consequently activated the cGAS-STING-IRF3 pathway and IFNβ production. These molecular events significantly enhanced the antitumor activity of NK and CIK against drug-pretreated sarcoma cells. The OCT4-positive cell fraction was enriched after chemotherapy. Noteworthy, NK/CIK cells efficiently killed both the drug-surviving bulk and CSC subpopulation. Conclusions. Trabectedin+olaparib treatment followed by NK/CIK-based immunotherapy is a promising therapeutic strategy against sarcomas, deserving further investigations.

Published in

The cGAS-STING pathway is a master regulator of OCT4 expression in persistent sarcoma cells and enhances cellular immunotherapy with NK and CIK lymphocytes

Giordano G, Merlini A, Capozzi F et al. · Cancer immunology, immunotherapy : CII 2025 · PMID 40986050 · doi:10.1007/s00262-025-04141-w

This dataset

Open GSE239639 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 GSE239639_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 PRJNA1000468 and SRA study SRP452457. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40986050) ↗

Study design

12 conditions, mostly in duplicate

DMR_CB ×2 DMR_NT ×2 DMR_OL ×2 DMR_T ×2 HT-1080_CB ×2 HT-1080_NT ×2 HT-1080_OL ×2 HT-1080_T ×2 +4 more

Supports a between-group comparison across 24 samples.

How we read this: 12 replicated groups read from 24 sample titles; they account for 24 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

GSM7669223 DMR_CB_1 DMR_CB
GSM7669224 DMR_CB_2 DMR_CB
GSM7669225 DMR_NT_1 DMR_NT
GSM7669226 DMR_NT_2 DMR_NT
GSM7669227 DMR_OL_1 DMR_OL
GSM7669228 DMR_OL_2 DMR_OL
GSM7669229 DMR_TR_1 DMR_T
GSM7669230 DMR_TR_2 DMR_T
GSM7669231 HT-1080_CB_1 HT-1080_CB
GSM7669232 HT-1080_CB_2 HT-1080_CB
GSM7669233 HT-1080_NT_1 HT-1080_NT
GSM7669234 HT-1080_NT_2 HT-1080_NT
GSM7669235 HT-1080_OL_1 HT-1080_OL
GSM7669236 HT-1080_OL_2 HT-1080_OL
GSM7669237 HT-1080_TR_1 HT-1080_T
GSM7669238 HT-1080_TR_2 HT-1080_T
GSM7669239 S018_CB_1 S018_CB
GSM7669240 S018_CB_2 S018_CB
GSM7669241 S018_NT_1 S018_NT
GSM7669242 S018_NT_2 S018_NT
GSM7669243 S018_OL_1 S018_OL
GSM7669244 S018_OL_2 S018_OL
GSM7669245 S018_TR_1 S018_T
GSM7669246 S018_TR_2 S018_T

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