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PARP inhibitor radiosensitization enhances anti-PD-L1 immunotherapy through depression of chemokine translation in small cell lung cancer

GSE233820 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/02/04 Platform GPL20795
At a glance

RNA-seq (gene expression) · human · 12 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)
Topic
Small cell lung cancerThis series is part of our curated briefing on it.
Samples
12 samples: 3 × SBC5, DMSO+0Gy vs 3 × SBC5, PARPi+0Gy vs 3 × SBC5, DMSO+4Gy vs 3 × SBC5, PARPi+4GyGroups 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
PARP inhibitor radiosensitization enhances anti-PD-L1 immunotherapy through stabilizing chemokine mRNA in small cell lung cancerNature communications · 2025
Summary (written by the submitters)
Immunotherapy (IO) is an effective therapeutic for various cancers however the benefits are modest for small cell lung cancer (SCLC). The poor response of SCLC to anti-PD-1/PD-L1 IO is due in part to the lack of cytotoxic T cells because of limited chemokine expression from SCLC tumors. Immunogenic radiosensitizers that enhance chemokine expression may be a promising strategy forward.
Read the full summary ↓
Here, we showed that the PARP inhibitor, olaparib, in combination with radiotherapy (RT) enhanced immune activation and anti-tumor efficacy in SCLC cell lines, patient-derived xenograft (PDX) and syngeneic mouse models, that was further pronounced with continued delivery of adjuvant olaparib. The combination treatment (olaparib with RT) activated the cGAS-STING pathway and increased the mRNA levels of the T cell chemoattractants, CCL5 and CXCL10. Interestingly, we found the combination treatment significantly downregulated expression of the mRNA translational repressor EIF4E2 to further increase chemokine CXCL10 protein levels via post-transcriptional stabilization of CXCL10 mRNA in its 3’ UTR region. We demonstrated the combination treatment augmented cytotoxic CD8+ T cell tumor infiltration and upregulated PD-L1 gene expression and protein levels. The incorporation of anti-PD-L1 IO with olaparib and RT significantly improved anti-tumor efficacy by protecting T cells from exhaustion. This study identified a novel mechanism of treatment-induced chemokine regulation that provides a rationale for the combination of PARP inhibitors, RT and anti-PD-L1 IO as a novel treatment strategy for SCLC.
Published in
PARP inhibitor radiosensitization enhances anti-PD-L1 immunotherapy through stabilizing chemokine mRNA in small cell lung cancer
Ran X, Wu BX, Vidhyasagar V et al. · Nature communications 2025 · PMID 40038278 · doi:10.1038/s41467-025-57257-z
This dataset
Open GSE233820 in finder → Find more human RNA-seq datasets → Small cell lung cancer landscape →
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 GSE233820_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 PRJNA978046 and SRA study SRP440491. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40038278) ↗
Study design
3 × SBC5, DMSO+0Gy vs 3 × SBC5, PARPi+0Gy vs 3 × SBC5, DMSO+4Gy vs 3 × SBC5, PARPi+4Gy

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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
More Small cell lung cancer datasets

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