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Molecular and cellular consequences of tumor-autonomous IL-6 signaling in intrahepatic cholangiocarcinoma

GSE320081 Homo sapiens (human) RNA-seq (gene expression) 36 samples Submitted 2026/08/20 Platform GPL21697
At a glance

RNA-seq (gene expression) · human · 36 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
CholangiocarcinomaThis series is part of our curated briefing on it.
Samples
36 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.
Summary (written by the submitters)
Background: High serum levels of interleukin-6 (IL-6) predict poor prognosis in intrahepatic cholangiocarcinoma (iCCA), a malignancy that often develops in a chronically inflamed milieu. Here, tumor cells are capable of autonomously producing and engaging autocrine IL-6 signaling, yet the consequences of this remain unknown. Objective: This study aims to explore the intra- and intercellular consequences of sustained, tumor-derived IL-6 signaling.
Read the full summary ↓
Design: We generated CRISPR-activated IL-6high patient-derived iCCA cell models and characterized them using RNA-sequencing and secretome analysis. Therapeutic vulnerabilities were determined with high-throughput drug screening, while the impact of tumor-conditioned media on the phenotype and function of circulating immune cells was assessed with high-dimensional flow cytometry. Spatial transcriptomic analysis (Visium HD) was performed on 14 resected tumors to quantify tumor-derived IL6 expression, cell type composition, and ligand-receptor interactions in the tumor microenvironment. Results: Chronic IL-6 signaling drives distinct transcriptional programs, metabolic vulnerabilities, and immunomodulatory effects. IL-6high tumor cells confer sensitivity to nicotinamide phosphoribosyltransferase (NAMPT) inhibition, leading to disrupted mitochondrial fitness and selective IL-6 downregulation. Chronic IL-6 signaling also alters the tumor secretome, which modulates immune cell composition and impairs cellular function, including the suppression of MER proto-oncogene tyrosine kinase (MerTK)-mediated macrophage efferocytosis. Spatial transcriptomic analysis confirms that tumor IL6 expression correlates with myeloid cell depletion, cancer-associated fibroblast (CAF) enrichment, and enhanced tumor-CAF communication. Conclusions: These findings uncover a multifaceted role for IL-6 in shaping tumor-intrinsic, microenvironmental, and macroenvironmental features, revealing novel molecular mechanisms and potential therapeutic vulnerabilities in iCCA.
This dataset
Open GSE320081 in finder → Find more human RNA-seq datasets → Cholangiocarcinoma 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 GSE320081_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 PRJNA1426350 and SRA study SRP678398. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Samples in this study

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+ 36 more — browse all 36 samples with per-sample file links →

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