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Transcriptional repression by HDAC3 mediates T cell exclusion from Kras mutant lung tumors [KL GEMM Treated Primary Tumors RNA-seq]

GSE277929 Mus musculus (mouse) RNA-seq (gene expression) 35 samples Submitted 2024/10/10 Platform GPL17021
At a glance

RNA-seq (gene expression) · mouse · 35 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
Mus musculus (mouse)
Samples
35 samples: 9 × KLtumors,combination,3weeks, vs 9 × KLtumors,entinostat,3weeks, vs 9 × KLtumors,vehicle,3weeks, vs 8 × KLtumors,trametinib,3weeks,Groups 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
Transcriptional repression by HDAC3 mediates T cell exclusion from Kras mutant lung tumorsProceedings of the National Academy of Sciences of the United States of America · 2024
Summary (written by the submitters)
Histone Deacetylase 3 (HDAC3) function in vivo is nuanced and directed in a tissue specific fashion. The importance of HDAC3 in Kras mutant lung tumors has recently been identified, but HDAC3 function in this context remains to be fully elucidated. Here, we identified HDAC3 as a lung tumor cell-intrinsic transcriptional regulator of the tumor immune microenvironment.
Read the full summary ↓
In Kras mutant lung cancer cells, we found that HDAC3 is a direct transcriptional repressor of a cassette of secreted chemokines, including Cxcl10. Genetic and pharmacological inhibition of HDAC3 robustly upregulated this gene set in human and mouse Kras, LKB1 (KL) and Kras, p53 (KP) mutant lung cancer cells through an NF-kB/p65-dependent mechanism. Using genetic engineered mouse models, we found that HDAC3 inactivation in vivo induced expression of this gene set selectively in lung tumors, and resulted in enhanced T-cell recruitment at least in part via Cxcl10. Furthermore, we found that inhibition of HDAC3 in the presence of Kras pathway inhibitors dissociated Cxcl10 expression from that of immunosuppressive chemokines, and that combination treatment of entinostat with trametinib enhanced T-cell recruitment into lung tumors in vivo. Finally, we showed that T-cells contribute to in vivo tumor growth control in the presence of entinostat and trametinib combination treatment. Together, our findings reveal that HDAC3 is a druggable endogenous repressor of T-cell recruitment into Kras mutant lung tumors.
Published in
Transcriptional repression by HDAC3 mediates T cell exclusion from Kras mutant lung tumors
McGuire CK, Meehan AS, Couser E et al. · Proceedings of the National Academy of Sciences of the United States of America 2024 · PMID 39388266 · doi:10.1073/pnas.2317694121
This dataset
Open GSE277929 in finder → Find more mouse 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 GSE277929_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 PRJNA1164765 and SRA study SRP534524. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39388266) ↗
Study design
9 × KLtumors,combination,3weeks, vs 9 × KLtumors,entinostat,3weeks, vs 9 × KLtumors,vehicle,3weeks, vs 8 × KLtumors,trametinib,3weeks,

Supports a between-group comparison across 35 samples.

How we read this: 4 replicated groups read from 35 sample titles; they account for 35 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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