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EZH2 INHIBITION ENHANCES T CELL IMMUNOTHERAPIES BY INDUCING LYMPHOMA IMMUNOGENICITY AND IMPROVING T CELL FUNCTION (CUT&RUN)

GSE278481 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 16 samples Submitted 2025/01/10 Platform GPL24247Platform GPL24676
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 16 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Samples
16 samples: 5 × PDX_DLBCL-EZB_vehicle_H3K27me3CnR vs 5 × PDX_DLBCL-EZB_tazemetostat_H3K27me3CnR vs 3 × tFL-P6_cellLine_DMSO_H3K27me3CnR vs 3 × tFL-P6_cellLine_tazemetostat_H3K27me3CnRGroups 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
EZH2 inhibition enhances T cell immunotherapies by inducing lymphoma immunogenicity and improving T cell functionCancer cell · 2025
Summary (written by the submitters)
While T cell immunotherapies have demonstrated effectiveness in a subset of patients with diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL), they are currently administered without guidance regarding whether the underlying biology or immunology is conducive to a durable response. Moreover, mechanisms explaining CAR-T resistance in B cell lymphomas remain largely unknown, and suitable systems to study lymphomas are currently unavailable, making it infeasible.
Read the full summary ↓
To address these unmet needs, we developed syngeneic animal models reflecting the genetics, epigenetics, and immunology of human FL and DLBCL. We show that treatment of these models with EZH2 inhibitors reprogrammed them to re-express T cell engagement genes and rendered them highly immunogenic. Notably, EZH2 inhibitors did not exhibit deleterious effects on T cells. Instead, they promoted a memory CAR CD8 phenotype and reduced exhaustion, resulting in a superior elimination of lymphoma B cells and decreased tumor burden. Intravital 2-photon imaging of transformed FL bearing mice showed that EZH2 inhibition increased the recruitment of CAR-T into the tumor microenvironment and enhanced the quality of interactions with lymphoma cells, leading to increased killing. Therefore, inhibition of EZH2 enhances CAR-T cell activity through direct effects on CAR-T cells, in addition to rendering lymphoma B cells immunogenic. This offers an innovative approach for enhancing the prognosis of patients with refractory B cell lymphomas, and is currently under evaluation in a clinical trial (NCT05934838)
Published in
EZH2 inhibition enhances T cell immunotherapies by inducing lymphoma immunogenicity and improving T cell function
Isshiki Y, Chen X, Teater M et al. · Cancer cell 2025 · PMID 39642889 · doi:10.1016/j.ccell.2024.11.006
This dataset
Open GSE278481 in finder → Find more ChIP / ATAC / CUT&Tag 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 GSE278481_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1167338 and SRA study SRP535828. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39642889) ↗
Study design
5 × PDX_DLBCL-EZB_vehicle_H3K27me3CnR vs 5 × PDX_DLBCL-EZB_tazemetostat_H3K27me3CnR vs 3 × tFL-P6_cellLine_DMSO_H3K27me3CnR vs 3 × tFL-P6_cellLine_tazemetostat_H3K27me3CnR

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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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