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Mitochondrial potential as a biomarker of T cell fitness and function in cancer immunotherapy

GSE315510 Homo sapiens (human) Single-cell RNA-seq 30 samples Submitted 2026/03/25 Platform GPL24676
At a glance

Single-cell RNA-seq · human · 30 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
30 samples: 24 distinct titles, 6 of them repeatedGroups 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)
Checkpoint inhibitors have transformed cancer treatment, yet predicting responses remains challenging. Mitochondrial quality decreases in tumor infiltrating lymphocytes and correlates with impaired anti-tumor immunity in animal models. Mitochondrial membrane potential (MMP) increases with T cell activation but may also indicate cellular dysfunction.
Read the full summary ↓
Here we assessed the MMP of tumor-associated T cells as an indicator of cell phenotypes and immunotherapy responses in Non-Small Cell Lung Carinoma and clear cell Renal Cell Carcinoma patients. Primary tumors were collected followed by analysis of peripheral blood mononuclear cells (PBMC) prior to and after three weeks on treatment with immune checkpoint inhibition (ICI). PBMC T cells were analyzed for MMP using tetramethylrhodamine ethyl ester (TMRE) and sorted into high and low populations. TCRβ and single cell RNA sequencing of primary tumors identified and characterized peripheral blood T cell clones associated with the tumor microenvironment. As anticipated, ICI therapy increased the frequency of effector T cells in patients who experienced clinical benefit. TMREhigh peripheral blood T cells with tumor-matching TCRβ sequences had elevated oxidative phosphorylation gene signatures. Gene signatures of stress and exhaustion, such as Tigit and Cmc1, were also elevated in the TMREhigh CD8 T cell populations while gene expression patterns in TMRElow cells suggested mitochondrial fitness and cell longevity. Importantly, clinical benefit from ICI was negatively correlated with the TMREhigh CD8 T cell gene expression signature. These findings highlight the presence of a T cell population of with elevated MMP that correlates with T cell exhaustion-like states and failed response to immunotherapy.
This dataset
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.

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 GSE315510_RAW.tar (it can run to tens of gigabytes).

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.

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1398172 and SRA study SRP659727. Searching any of these in the dataset finder brings you back here.

Study design
24 distinct titles, 6 of them repeated
Lung, Partial disease, Pre-treatment, TMRE hi… ×2 Lung, Partial disease, Pre-treatment, TMRE lo… ×2 Lung, Partial disease, Post-treatment initiat… ×2 Lung, Partial disease, Post-treatment initiat… ×2 Lung, Stable disease, Pre-treatment, TMRE hig… ×2 Lung, Stable disease, Post-treatment initiati… ×2

How we read this: Read from 30 sample titles: 24 distinct titles with little repetition. 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
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