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Baseline Immune State and T cell Clonal Kinetics are Associated with Response to CAR-T Therapy in Large B-cell Lymphoma

GSE273170 Homo sapiens (human) Single-cell RNA-seq 81 samples Submitted 2024/08/12 Platform GPL24676
At a glance

Single-cell RNA-seq · human · 81 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
81 samples: 12 conditions, mostly with about 5 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
Baseline immune state and T-cell clonal kinetics are associated with durable response to CAR-T therapy in large B-cell lymphomaBlood · 2024
Summary (written by the submitters)
Engineered cellular therapy with CD19-targeting chimeric antigen receptor T-cells (CAR-T) has revolutionized outcomes for patients with relapsed/refractory Large B-Cell Lymphoma (LBCL), but the cellular and molecular features associated with response remain largely unresolved.
Read the full summary ↓
We analyzed serial peripheral blood samples ranging from day of apheresis (day -28/baseline) to 28 days after CAR-T infusion from 50 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) by integrating single cell RNA and TCR sequencing (scRNA-seq/scTCR-seq), flow cytometry, and mass cytometry (CyTOF) to characterize features associated with response to CAR-T. Pretreatment patient characteristics associated with response included presence of B cells and increased lymphocyte-to-monocyte ratio (ALC/AMC). Infusion products from responders were enriched for clonally expanded, highly activated CD8+ T cells. We expanded these observations to 99 patients from the ZUMA-1 cohort and identified a subset of patients with elevated baseline B cells, 80% of whom were complete responders. We integrated B cell proportion and ALC/AMC into a two-factor predictive model and applied this model to the ZUMA-1 cohort. Estimated progression free survival (PFS) at 1 year in patients meeting one or both criteria was 65% versus 31% for patients meeting neither criterion. Our results suggest that patients’ immunologic state at baseline affects likelihood of response to CAR-T through both modulation of the T cell apheresis product composition and promoting a more favorable circulating immune compartment prior to therapy. These baseline immunologic features, measured readily in the clinical setting prior to CAR-T, can be applied to predict response to therapy.
Published in
Baseline immune state and T-cell clonal kinetics are associated with durable response to CAR-T therapy in large B-cell lymphoma
Maurer K, Grabski IN, Houot R et al. · Blood 2024 · PMID 39241199 · doi:10.1182/blood.2024024381
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 GSE273170_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 PRJNA1140521. Searching any of these in the dataset finder brings you back here.

Study design
12 conditions, mostly with about 5 replicates each
PBMCs, RNA, Day 7, CA ×10 PBMCs, RNA, Day 14, CA ×10 PBMCs, TCR, Day 7, CA ×9 PBMCs, TCR, Day 14, CA ×9 PBMCs, ADT, Day 7, CA ×8 PBMCs, ADT, Day 14, CA ×8 Infusion product, RNA, CA ×5 Infusion product, TCR, CA ×5 +4 more

Supports a between-group comparison across 81 samples.

How we read this: 12 replicated groups read from 81 sample titles; they account for 81 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

+ 41 more — browse all 81 samples with per-sample file links →

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