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Epigenetic remodeling in sarcoma promotes T cell infiltration via modulation of the Hippo pathway (human)

GSE312026 Homo sapiens (human) RNA-seq (gene expression) 21 samples Submitted 2026/04/15 Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 21 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)
Topic
OsteosarcomaThis series is part of our curated briefing on it.
Samples
21 samples: 7 conditions, mostly in triplicateGroups 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
Epigenetic remodeling in sarcoma promotes T-cell infiltration via modulation of the Hippo pathwayJournal for immunotherapy of cancer · 2026
Summary (written by the submitters)
Immunotherapy in osteosarcoma remains limited by insufficient T cell infiltration. Considering the importance of epigenetics in sarcomagenesis, the impact of histone modifications in shaping the immune microenvironment was investigated. Using patient-derived ex vivo spheroids and in vivo metastatic osteosarcoma models, we found that pharmacological elevation of H3K27ac by the histone deacetylase 1/3 inhibitor entinostat promotes CD8⁺ T-cell activation, cytotoxicity, and the recruitment of CD8+CD103⁺ tissue-resident memory (TRM) T cells.
Read the full summary ↓
Mechanistically, these immune-boosting effects are triggered by a Hippo pathway switch, in which Yes-associated protein 1 (YAP1) is suppressed and vestigial-like family member 3 (VGLL3) is induced, thereby rewiring transcription. Furthermore, we identified that VGLL3/CD103 signatures predict a response to anti-PD-1 treatment in sarcoma patients, and that combining H3K27ac induction with anti-PD-1 further augments T cell-mediated killing in ex vivo autologous patient-derived spheroid models. Our findings reveal an epigenetic-Hippo-immunomodulatory axis in osteosarcoma that also extends to other sarcomas, providing a rationale for incorporating epigenetic preconditioning with immunotherapy to improve patient outcomes and pointing towards novel biomarkers for treatment guidance.
Published in
Epigenetic remodeling in sarcoma promotes T-cell infiltration via modulation of the Hippo pathway
Cruz De Los Santos M, Chen Y, González De Zárate A et al. · Journal for immunotherapy of cancer 2026 · PMID 41922083 · doi:10.1136/jitc-2025-014601
This dataset
Open GSE312026 in finder → Find more human RNA-seq datasets → Osteosarcoma landscape →
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 GSE312026_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 PRJNA1372084 and SRA study SRP650407. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41922083) ↗
Study design
7 conditions, mostly in triplicate
MFS1_DMSO ×3 MFS1_ENT ×3 CBOS1_DMSO ×3 CBOS1_ENT ×3 MFS1_SC ×3 MFS1_YAP1 ×3 MFS1_VGLL3 ×3

Supports a between-group comparison across 21 samples.

How we read this: 7 replicated groups read from 21 sample titles; they account for 21 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
More Osteosarcoma datasets

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