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FOXO1 is a master regulator of CAR T memory programming [RNA_Dual_OE-KO]

GSE255413 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2024/02/29 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 12 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
Homo sapiens (human)
Samples
12 samples: 2 × CD19.28Z_FOXO1_OE_AAVS1_KO_Donor_TMP vs 2 × CD19.28Z_NGFR_OE_AAVS1_KO_Donor_TMP vs 2 × CD19.28Z_FOXO1_OE_TCF7_KO_Donor_TMP vs 2 × CD19.28Z_NGFR_OE_TCF7_KO_Donor_TMPGroups 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
FOXO1 is a master regulator of memory programming in CAR T cellsNature · 2024
Summary (written by the submitters)
Poor CAR T persistence limits CAR T cell therapies for B cell malignancies and solid tumors1,2. The expression of memory-associated genes such as TCF7 (protein name TCF1) is linked to response and long-term persistence in patients3–7, thereby implicating memory programs in therapeutic efficacy. Here, we demonstrate that the pioneer transcription factor, FOXO1, is responsible for promoting memory programs and restraining exhaustion in human CAR T cells.
Read the full summary ↓
Pharmacologic inhibition or gene editing of endogenous FOXO1 in human CAR T cells diminished the expression of memory-associated genes, promoted an exhaustion-like phenotype, and impaired antitumor activity in vitro and in vivo. FOXO1 overexpression induced a gene expression program consistent with T cell memory and increased chromatin accessibility at FOXO1 binding motifs. FOXO1-overexpressing cells retained function, memory potential, and metabolic fitness during settings of chronic stimulation and exhibited enhanced persistence and antitumor activity in vivo. In contrast, TCF1 overexpression failed to enforce canonical memory programs or enhance CAR T cell potency. Importantly, endogenous FOXO1 activity correlated with CAR T and TIL responses in patients, underscoring its clinical relevance in cancer immunotherapy. Our results demonstrate that memory reprogramming through FOXO1 can enhance the persistence and potency of human CAR T cells and highlights the utility of pioneer factors, which bind condensed chromatin and induce local epigenetic remodeling, for optimizing therapeutic T cell states.
Published in
FOXO1 is a master regulator of memory programming in CAR T cells
Doan AE, Mueller KP, Chen AY et al. · Nature 2024 · PMID 38600391 · doi:10.1038/s41586-024-07300-8
This dataset
Open GSE255413 in finder → Find more human 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 GSE255413_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 PRJNA1074824 and SRA study SRP489007. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38600391) ↗
Study design
2 × CD19.28Z_FOXO1_OE_AAVS1_KO_Donor_TMP vs 2 × CD19.28Z_NGFR_OE_AAVS1_KO_Donor_TMP vs 2 × CD19.28Z_FOXO1_OE_TCF7_KO_Donor_TMP vs 2 × CD19.28Z_NGFR_OE_TCF7_KO_Donor_TMP

Supports a between-group comparison across 8 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 8 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
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