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Expansion of Tumor-Infiltrating CD8+ T Cell Clonotypes Occurs in the Spleen in Response to Immune Checkpoint Blockade

GSE270050 Mus musculus (mouse) Single-cell RNA-seq 29 samples Submitted 2024/07/19 Platform GPL24247Platform GPL21626
At a glance

Single-cell RNA-seq · mouse · 29 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
Mus musculus (mouse)
Samples
29 samples: 8 conditions, mostly in duplicateGroups 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)
Immune checkpoint blockade (ICB) enhances tumor-reactive T cell responses against cancer, leading to long-term tumor control and survival in a fraction of patients. Given the increasingly recognized complexity of CD8+ T cell differentiation that occurs in response to chronic antigen stimulation, it remains unclear precisely which T cell differentiation states are critical for the response to ICB, as well as the anatomic sites at which ICB-mediated reinvigoration of these T cells occurs.
Read the full summary ↓
We used paired single-cell RNA and T cell receptor (TCR) sequencing to profile endogenous, tumor-reactive CD8+ T cells isolated from tumors, tumor-draining lymph nodes, and spleens of mice treated with ICB. We identified an intermediate-exhausted population of T cells in the spleen which underwent the greatest expansion in response to ICB and gave rise to the majority of tumor-infiltrating clonotypes. Increasing concentrations of systemic antigen perturbed the differentiation of this phenotype towards an exhausted_KLR state, while a lack of cross-presentation of tumor-derived antigen blunted differentiation in the spleen. We identified an analogous population of exhausted_KLR CD8+ T cells in matched human tumor and blood samples that exhibited diminished tumor-trafficking ability. Collectively, our data demonstrate the critical role of antigen density within the spleen in coordinating the differentiation and expansion of tumor-infiltrating T cell clonotypes in response to ICB.
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 GSE270050_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 PRJNA1124914 and SRA study SRP514351. Searching any of these in the dataset finder brings you back here.

Study design
8 conditions, mostly in duplicate
INT ×4 CBT_HTO_Spleen ×3 CBT_DEG_Spleen ×3 KL ×3 Untreated_HTO_Spleen ×2 CBT_HTO_TdLN ×2 Untreated_DEG_Spleen ×2 CBT_DEG_TdLN ×2 +8 more

Supports a between-group comparison across 21 samples.

How we read this: 8 replicated groups read from 29 sample titles; they account for 21 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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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.