GEO series

Reshaping the Tumor Microenvironment of KRASG12D Pancreatic Ductal Adenocarcinoma with combined SOS1 and MEK Inhibition for Improved Immunotherapy Response

GSE264527 Mus musculus (mouse) Single-cell RNA-seq 21 samples Submitted 2024/04/22 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 21 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: 21 samples: 6 conditions, mostly with about 4 replicates eachGroups 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: Reshaping the Tumor Microenvironment of KRASG12D Pancreatic Ductal Adenocarcinoma with Combined SOS1 and MEK Inhibition for Improved Immunotherapy ResponseCancer research communications · 2024

Summary (written by the submitters)

KRAS inhibitors have demonstrated exciting pre-clinical and clinical responses, although resistance occurs rapidly. Here, we investigate the effects of KRAS-targeting therapies on the tumor microenvironment using a library of KRASG12D, p53 mutant, murine PDAC-derived cell lines (KPCY) to leverage immune-oncology combination strategies for long-term tumor efficacy.

Read the full summary ↓

Our findings show that SOS1 and MEK inhibitors (SOS1i+MEKi) suppressed tumor growth in syngeneic models and increased intra-tumoral CD8+ T cells without durable responses. scRNA-sequencing revealed an increase in inflammatory cancer associated fibroblasts (iCAFs), M2 macrophages, and a decreased dendritic cell quality that ultimately resulted in a highly immunosuppressive microenvironment driven by IL6+ iCAFs. Agonist CD40 treatment was effective to revert macrophage polarization and overcome the lack of mature antigen presenting DCs after SOS1i+MEKi therapy. Treatment increased the overall survival of KPCY tumor-bearing mice. The addition of checkpoint blockade to SOS1i+MEKi combination resulted in tumor free mice with established immune memory. Our data suggests that KRAS inhibition affects myeloid cell maturation and highlights the need for combining KRAS cancer-targeted therapy with myeloid activation to enhance and prolong anti-tumor effects.

Published in

Reshaping the Tumor Microenvironment of KRASG12D Pancreatic Ductal Adenocarcinoma with Combined SOS1 and MEK Inhibition for Improved Immunotherapy Response

Norgard RJ, Budhani P, O'Brien SA et al. · Cancer research communications 2024 · PMID 38727236 · doi:10.1158/2767-9764.CRC-24-0172

This dataset

Open GSE264527 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 GSE264527_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 PRJNA1103078 and SRA study SRP503261. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38727236) ↗

Study design

6 conditions, mostly with about 4 replicates each

TC3, SOS1i+MEKi, tumo ×4 TC4, SOS1i+MEKi, tumo ×4 TC5, SOS1i+MEKi, tumo ×4 TC3, Vehicle, tumo ×3 TC4, Vehicle, tumo ×3 TC5, Vehicle, tumo ×3

Supports a between-group comparison across 21 samples.

How we read this: 6 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

GSM8219542 TC3, Vehicle, tumor1 TC3, Vehicle, tumo
GSM8219543 TC3, Vehicle, tumor2 TC3, Vehicle, tumo
GSM8219544 TC3, Vehicle, tumor3 TC3, Vehicle, tumo
GSM8219545 TC3, SOS1i+MEKi, tumor1 TC3, SOS1i+MEKi, tumo
GSM8219546 TC3, SOS1i+MEKi, tumor2 TC3, SOS1i+MEKi, tumo
GSM8219547 TC3, SOS1i+MEKi, tumor3 TC3, SOS1i+MEKi, tumo
GSM8219548 TC3, SOS1i+MEKi, tumor4 TC3, SOS1i+MEKi, tumo
GSM8219549 TC4, Vehicle, tumor1 TC4, Vehicle, tumo
GSM8219550 TC4, Vehicle, tumor2 TC4, Vehicle, tumo
GSM8219551 TC4, Vehicle, tumor3 TC4, Vehicle, tumo
GSM8219552 TC4, SOS1i+MEKi, tumor1 TC4, SOS1i+MEKi, tumo
GSM8219553 TC4, SOS1i+MEKi, tumor2 TC4, SOS1i+MEKi, tumo
GSM8219554 TC4, SOS1i+MEKi, tumor3 TC4, SOS1i+MEKi, tumo
GSM8219555 TC4, SOS1i+MEKi, tumor4 TC4, SOS1i+MEKi, tumo
GSM8219556 TC5, Vehicle, tumor1 TC5, Vehicle, tumo
GSM8219557 TC5, Vehicle, tumor2 TC5, Vehicle, tumo
GSM8219558 TC5, Vehicle, tumor3 TC5, Vehicle, tumo
GSM8219559 TC5, SOS1i+MEKi, tumor1 TC5, SOS1i+MEKi, tumo
GSM8219560 TC5, SOS1i+MEKi, tumor2 TC5, SOS1i+MEKi, tumo
GSM8219561 TC5, SOS1i+MEKi, tumor3 TC5, SOS1i+MEKi, tumo
GSM8219562 TC5, SOS1i+MEKi, tumor4 TC5, SOS1i+MEKi, tumo

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.