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Inhibiting B-cell-mediated Immunosuppression to Enhance the Immunotherapy Efficacy in Hepatocellular Carcinoma

GSE301030 Mus musculus (mouse) RNA-seq (gene expression) 54 samples Submitted 2025/10/26 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 54 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
Mus musculus (mouse)
Samples
54 samples
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
Inhibiting B cells enhances the efficacy of STING agonism or immune checkpoint blockade in hepatocellular carcinomaNature communications · 2025
Summary (written by the submitters)
Immunotherapy benefits only a minority of hepatocellular carcinoma (HCC) patients due to immune checkpoint blockade (ICB) resistance, and agonists of the stimulator of interferon genes (STING) also showed limited efficacy despite their immune-stimulating properties. Here we show that increased intratumoral B cells mediate the resistance to ICB and STING agonism.
Read the full summary ↓
In the preclinical models with liver fibrosis that mimic human HCCs, tumors treated by anti-PD-1 ICB or a STING agonist (BMS-986301) showed more B-cell infiltration. STING agonism increased circulating IL-10 and intratumoral infiltration by B cells, including B cells expressing T-cell immunoglobulin and mucin domain 1 (TIM-1), and promoted the formation of tertiary lymphoid structure (TLS)-like structures, especially in the peritumoral areas. Strikingly, adding B cell depletion to ICB or STING agonism treatment significantly increased survival. Unlike ICB, STING agonism also had a pronounced anti-metastatic activity. In addition, the combination of STING agonism and TIM-1 blockade augmented B cell differentiation and antigen presentation in vitro and improved the anti-tumor effects in murine HCC in vivo. This approach decreased TIM-1+ B cells in the tumor and shifted B cells to higher expression of CD86 and MHC class II, enhancing their antigen presentation capability and further boosting the antitumor efficacy of CD8+ cytotoxic T cells. Our findings demonstrate that B cells are associated with ICB- and STING-mediated therapy resistance, and that depleting B cells or targeting TIM-1 enhances both innate and acquired therapeutic efficacy in HCC.
Published in
Inhibiting B cells enhances the efficacy of STING agonism or immune checkpoint blockade in hepatocellular carcinoma
Liu X, Liu Z, Zhu C et al. · Nature communications 2025 · PMID 41360802 · doi:10.1038/s41467-025-66581-3
This dataset
Open GSE301030 in finder → Find more mouse 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 GSE301030_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 PRJNA1283102 and SRA study SRP595569. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41360802) ↗
Samples in this study

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