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Longitudinal single-cell immunoprofiling links durable CAR T response to sustained activation and clonotypic expansion of the native cytotoxic T cell repertoire

GSE290722 Homo sapiens (human) Single-cell RNA-seq 184 samples Submitted 2025/03/04 Platform GPL24676
At a glance

Single-cell RNA-seq · human · 184 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism
Homo sapiens (human)
Samples
184 samples: 8 conditions, mostly with about 32 replicates eachGroups 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.
Paper
Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoireNature communications · 2025
Summary (written by the submitters)
CD19-directed chimeric antigen receptor (CAR) T-cell therapy has transformed outcomes for patients with relapsed/refractory large B-cell lymphoma (LBCL), yet the mechanisms underlying durable remission remain incompletely understood. While CAR T-cell persistence is associated with response, long-term remission can occur despite rapid CAR T clearance, suggesting the involvement of additional immune mechanisms.
Read the full summary ↓
To investigate the role of the native T-cell repertoire in shaping response durability, we performed single-cell RNA and TCR sequencing (scRNA-seq/scTCR-seq) on longitudinal peripheral blood samples from LBCL patients treated with axicabtagene ciloleucel (axi-cel) in the ZUMA-1 trial. We compared immune landscapes and clonotypic dynamics among patients achieving durable remission (>1 year), those experiencing early relapse (<6 months), and those with refractory disease. Patients with long-term remission exhibited increased cytotoxic, proinflammatory, and proliferative native T-cell subsets, while early relapse was associated with immunoregulatory populations that may suppress T-cell activation. TCR profiling revealed robust clonotypic expansion of native cytotoxic T cells post-infusion in durable responders, with expansion patterns strongly predicting clinical outcomes. Notably, TCR screens did not identify known viral targets, suggesting tumor-specific immunity may mediate ongoing remission. These findings propose native T-cell clonotypic expansion as a key determinant of durable response to CAR T therapy and highlight its predictive potential for long-term clinical outcomes.
Published in
Durable response to CAR T is associated with elevated activation and clonotypic expansion of the cytotoxic native T cell repertoire
Cheloni G, Karagkouni D, Pita-Juarez Y et al. · Nature communications 2025 · PMID 40410132 · doi:10.1038/s41467-025-59904-x
This dataset
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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 GSE290722_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: 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 PRJNA1229630. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40410132) ↗
Study design
8 conditions, mostly with about 32 replicates each
PBMCs, RNA, Leukapheresis, P ×32 PBMCs, TCR, Leukapheresis, P ×32 PBMCs, RNA, 4wk post-CAR T, P ×27 PBMCs, TCR, 4wk post-CAR T, P ×27 PBMCs, RNA, 6mo post-CAR T, P ×17 PBMCs, TCR, 6mo post-CAR T, P ×17 PBMCs, RNA, 12mo post-CAR T, P ×16 PBMCs, TCR, 12mo post-CAR T, P ×16

Supports a between-group comparison across 184 samples.

How we read this: 8 replicated groups read from 184 sample titles; they account for 184 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

+ 144 more — browse all 184 samples with per-sample file links →

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