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Targeting PRC2 enhances the antitumor cytotoxic capacity of anti-CD19 CAR-T cells against hematological malignancies

GSE277818 Homo sapiens (human) RNA-seq (gene expression) 12 samples Submitted 2025/02/03 Platform GPL30173
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: 4 × CAR-T Cells, A395_ID vs 4 × CAR-T Cells, DMSO_ID vs 4 × CAR-T Cells, GSK343_IDGroups 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
Targeting PRC2 Enhances the Cytotoxic Capacity of Anti-CD19 CAR T Cells against Hematologic MalignanciesCancer research · 2025
Summary (written by the submitters)
Chimeric Antigen Receptor (CAR) T cell therapy was adopted as a clinical modality for patients with relapsed/refractory hematological malignancies. Despite the clinical efficacy of CAR-T cell therapy, a considerable fraction of patients still relapses during the first months following CAR-T cell infusion. The limited CAR-T cell efficiency is thought to relate to epigenetic mechanisms involved in T cell suppression and dysfunction.
Read the full summary ↓
Here, screening of multiple epigenetic inhibitors revealed that targeting PRC2 consistently enhanced the cytotoxic/effector phenotype of CD8 T cells. Notably, PRC2 inhibition promoted the differentiation of GZMB+ effector memory 19BBζ CAR-T cells and enhanced their antitumor activity both in vitro and in vivo. Consistent with their long-lasting antitumor activity, PRC2-inhibited 19BBζ CAR-T cells did not exhibit any signs of dysfunctionality/exhaustion. Furthermore, TCR restimulation along with PRC2 inhibition of patient-derived anti-CD19 CAR-T cells also induced the development of GZMB+ effector memory cells and elicited potent antitumor responses against CD19+ Daudi cells. In line with this, the gene signature derived from in-house PRC2-inhibited 19BBζ CAR-T cells was enriched in tisagenlecleucel (tisa-cel) BBζ CAR-T cell therapy responders with large B-cell lymphoma. Collectively, our results demonstrated that targeting PRC2 may be a promising approach to enhance a functional effector program in CAR-T cells against hematological malignancies.
Published in
Targeting PRC2 Enhances the Cytotoxic Capacity of Anti-CD19 CAR T Cells against Hematologic Malignancies
Rodrigues Carvalho ML, de Oliveira Andrade C, Cabral-Piccin MP et al. · Cancer research 2025 · PMID 39970330 · doi:10.1158/0008-5472.CAN-24-1643
This dataset
Open GSE277818 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 GSE277818_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 PRJNA1164268 and SRA study SRP534254. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39970330) ↗
Study design
4 × CAR-T Cells, A395_ID vs 4 × CAR-T Cells, DMSO_ID vs 4 × CAR-T Cells, GSK343_ID

Supports a between-group comparison across 12 samples.

How we read this: 3 replicated groups read from 12 sample titles; they account for 12 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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