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Loss of tumor cell MHC Class II drives MAPK-inhibitor insensitivity of BRAF-mutant anaplastic thyroid cancers [ATAC-seq]

GSE302630 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 16 samples Submitted 2025/08/08 Platform GPL24247
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 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
Mus musculus (mouse)
Samples
16 samples: 8 conditions, mostly in duplicateGroups 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
Loss of tumor cell MHC class II drives MAPK inhibitor insensitivity of BRAF-mutant anaplastic thyroid cancersThe Journal of clinical investigation · 2025
Summary (written by the submitters)
Cancer cells present neoantigens dominantly through MHC class I (MHCI) to drive tumor rejection through cytotoxic CD8+ T-cells. There is growing recognition that a subset of tumors express MHC class II (MHCII), causing recognition of antigens by TCRs of CD4+ T-cells that contribute to the anti-tumor response. We find that mouse BrafV600E-driven anaplastic thyroid cancers (ATC) respond markedly to the RAF + MEK inhibitors dabrafenib and trametinib (dab/tram) and that this is associated with upregulation of MhcII in cancer cells and increased CD4+ T-cell infiltration.
Read the full summary ↓
A subset of recurrent tumors lose MhcII expression due to silencing of Ciita, the master transcriptional regulator of MhcII, despite preserved interferon gamma signal transduction, which can be rescued by EZH2 inhibition. Orthotopically-implanted Ciita-/- and H2-Ab1-/- ATC cells into immune competent mice become unresponsive to the MAPK inhibitors. Moreover, depletion of CD4+, but not CD8+ T-cells, also abrogates response to dab/tram. These findings implicate MHCII-driven CD4+ T cell activation as a key determinant of the response of Braf-mutant ATCs to MAPK inhibition.
Published in
Loss of tumor cell MHC class II drives MAPK inhibitor insensitivity of BRAF-mutant anaplastic thyroid cancers
Tiedje V, Greenberg J, Qin T et al. · The Journal of clinical investigation 2025 · PMID 40828595 · doi:10.1172/JCI191781
This dataset
Open GSE302630 in finder → Find more mouse 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 GSE302630_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 PRJNA1291619 and SRA study SRP601124. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40828595) ↗
Study design
8 conditions, mostly in duplicate
ATAC_Prim_B92_IFNG ×2 ATAC_Prim_B92_IFNGandTram ×2 ATAC_Prim_B92_Tram ×2 ATAC_Prim_B92_Vehicle ×2 ATAC_Rec_B36934_IFNG ×2 ATAC_Rec_B36934_IFNGandTram ×2 ATAC_Rec_B36934_Tram ×2 ATAC_Rec_B36934_Vehicle ×2

Supports a between-group comparison across 16 samples.

How we read this: 8 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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