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Host MTDH orchestrates liver lipid metabolism and CD8+ T cells to suppress antitumor immunity [Hepatocytes]

GSE299133 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2025/12/31 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 18 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
18 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.
Summary (written by the submitters)
Cancer affects the function of distant organs beyond metastasis, conversely, dysfunction in distant organs can also impact tumor progression. However, the mechanisms underlying these interactions remains poorly understood. Here, we uncover that metadherin (MTDH), previously identified as a cancer metastatic gene, expressed in different host tissues, manipulates systemic lipid metabolism to control CD8+ T cell-mediated antitumor immunity.
Read the full summary ↓
Genetic ablation of MTDH in host tissues significantly suppresses tumor growth and lung metastasis. Mechanistically, MTDH loss in hepatocytes prevents tumor environment-driven dysfunction of lipid metabolism. MTDH deficiency in hepatocytes increases PPARa-mediated lipid oxidation, resulting in reduced systemic lipid levels. Moreover, reduced systemic lipid levels metabolically reprogram MTDH knockout (KO) tumor-infiltrating CD8+ T cells by increasing mitochondrial biogenesis and resistance to lipid peroxidation-induced death. This increased metabolic fitness enhances the effector function of MTDH KO tumor-infiltrating CD8+ T, triggering ASCL4-depedent ferroptosis in tumor cells, contributing to tumor suppression. Targeting host MTDH efficiently synergizes with anti-PD-1 therapy across colorectal and metastatic breast cancer models, providing a promising therapeutic strategy for immunotherapy non-responsive cancers. Thus, our study identifies MTDH as an essential bridge connecting tumor and distant liver communications through metabolic reprogramming, revealing a previously unknown mechanism by which cancer is regulated as a systemic disease.
This dataset
Open GSE299133 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 GSE299133_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 PRJNA1272630 and SRA study SRP590249. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
6 conditions, mostly in triplicate
hepatocytes from MTDH KO mice, treatment with… ×3 hepatocytes from MTDH WT mice, treatment with… ×3 hepatocytes from MTDH KO mice, treatment with… ×3 hepatocytes from MTDH WT mice, treatment with… ×3 hepatocytes from MTDH KO mice, treatment with… ×3 hepatocytes from MTDH WT mice, treatment with… ×3

Supports a case/control comparison: 3 samples read as cases, 6 as controls.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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
Datasets on a similar topic

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