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Type I interferon signaling pathway enhances immune-checkpoint inhibition in KRAS mutant lung tumors [LCM]

GSE274351 Mus musculus (mouse) Single-cell RNA-seq 18 samples Submitted 2024/08/12 Platform GPL21626

At a glance

Single-cell RNA-seq · mouse · 18 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Mus musculus (mouse)
Samples: 18 samples: 5 × K adenoma vs 5 × KP adenoma vs 4 × KL adenoma vs 4 × Normal lungGroups 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: Type I interferon signaling pathway enhances immune-checkpoint inhibition in KRAS mutant lung tumorsProceedings of the National Academy of Sciences of the United States of America · 2024

Summary (written by the submitters)

Lung cancer is the leading cause of cancer mortality worldwide. KRAS oncogenes are responsible for at least a quarter of lung adenocarcinomas, the main subtype of lung cancer. After four decades of intense research, selective inhibitors of KRAS oncoproteins are finally reaching the clinic. Yet, their effect on overall survival is limited due to the rapid appearance of drug resistance, a likely consequence of the high intratumoral heterogeneity characteristic of these tumors.

Read the full summary ↓

In this study, we have attempted to identify those functional alterations that result from KRAS oncoprotein expression during the earliest stages of tumor development. Such functional changes are likely to be maintained during the entire process of tumor progression regardless of additional co-occurring mutations. Single-cell RNA sequencing analysis of murine alveolar type 2 cells expressing a resident Kras oncogene revealed impairment of the type I interferon pathway, a feature maintained throughout tumor progression. This alteration was also present in advanced murine and human tumors harboring additional mutations in the p53 or LKB1 tumor suppressors. Restoration of type I interferon (IFN) signaling by IFN-beta or constitutive active stimulator of interferon genes (STING) expression had a profound influence on the tumor microenvironment, switching them from immunologically “cold” to immunologically “hot” tumors. Therefore, enhancement of the type I IFN pathway predisposes KRAS mutant lung tumors to immunotherapy treatments, regardless of co-occurring mutations in p53 or LKB1.

Published in

Type I interferon signaling pathway enhances immune-checkpoint inhibition in KRAS mutant lung tumors

Fernández-García F, Fernández-Rodríguez A, Fustero-Torre C et al. · Proceedings of the National Academy of Sciences of the United States of America 2024 · PMID 39186651 · doi:10.1073/pnas.2402913121

This dataset

Open GSE274351 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 GSE274351_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1146028 and SRA study SRP525127. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39186651) ↗

Study design

5 × K adenoma vs 5 × KP adenoma vs 4 × KL adenoma vs 4 × Normal lung

Supports a between-group comparison across 18 samples.

How we read this: 4 replicated groups read from 18 sample titles; they account for 18 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

GSM8447755 K adenoma 1 K adenoma
GSM8447756 K adenoma 2 K adenoma
GSM8447757 K adenoma 3 K adenoma
GSM8447758 K adenoma 4 K adenoma
GSM8447759 K adenoma 5 K adenoma
GSM8447760 KP adenoma 1 KP adenoma
GSM8447761 KP adenoma 2 KP adenoma
GSM8447762 KP adenoma 3 KP adenoma
GSM8447763 KP adenoma 4 KP adenoma
GSM8447764 KP adenoma 5 KP adenoma
GSM8447765 KL adenoma 1 KL adenoma
GSM8447766 KL adenoma 2 KL adenoma
GSM8447767 KL adenoma 3 KL adenoma
GSM8447768 KL adenoma 4 KL adenoma
GSM8447769 Normal lung 1 Normal lung
GSM8447770 Normal lung 2 Normal lung
GSM8447771 Normal lung 3 Normal lung
GSM8447772 Normal lung 4 Normal lung

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