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Series GSE210038 Query DataSets for GSE210038
Status Public on Jun 26, 2023
Title Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear-cell renal cell carcinoma [scRNA-seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Immune checkpoint inhibitors (ICI) represent the cornerstone for treatment of patients with metastatic clear-cell renal cell carcinoma (ccRCC). Despite a favorable response for a subset of patients, others experience primary progressive disease highlighting the need to precisely understand plasticity of cancer cells and their crosstalk with the microenvironment to better predict therapeutic response and personalize treatment. Single-cell RNA sequencing of ccRCC at different disease stages and normal adjacent tissue (NAT) from patients identified 46 cell populations, including 5 tumor subpopulations, characterized by distinct transcriptional signatures representing an epithelial to mesenchymal transition gradient and a novel inflamed state. Deconvolution of the tumor and microenvironment signatures in public datasets and in data from the BIONIKK clinical trial (NCT02960906) revealed a strong correlation between mesenchymal-like ccRCC cells and myofibroblastic cancer-associated fibroblasts (myCAFs), which are both enriched in metastases and correlate with poor patient survival. Spatial transcriptomics and multiplex immune staining uncovered spatial proximity of mesenchymal-like ccRCC cells and myCAFs at the tumor-NAT interface. Moreover, enrichment in myCAFs was associated with primary resistance to ICI therapy in the BIONIKK clinical trial. This data highlights the epithelial-mesenchymal plasticity of ccRCC cancer cells and their relationship with myCAFs, a critical component of the microenvironment associated with poor outcome and ICI resistance.
 
Overall design Seven tumoral and two normal adjacent tissue samples from patients presenting clear-cell Renal Cell Carcinoma were analyzed by single-cell RNA sequencing.
 
Contributor(s) Helleux A, Davidson G, Malouf G, Davidson I
Citation(s) 37335139
Submission date Jul 29, 2022
Last update date Jun 29, 2023
Contact name Guillaume Davidson
E-mail(s) davidsoy@igbmc.fr
Organization name I.G.B.M.C. - Institut de génétique et de biologie moléculaire et cellulaire
Street address 1 Rue Laurent Fries
City Illkirch-Graffenstaden
ZIP/Postal code 67400
Country France
 
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL21697 NextSeq 550 (Homo sapiens)
Samples (9)
GSM6415686 Tumour 1 (T1)
GSM6415687 Tumour 2 (T2)
GSM6415688 Tumour 3 (T3)
This SubSeries is part of SuperSeries:
GSE210042 Mesenchymal-like tumor cells and myofibroblastic cancer-associated fibroblasts are associated with progression and immunotherapy response of clear-cell renal cell carcinoma
Relations
BioProject PRJNA863568

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE210038_RAW.tar 99.2 Mb (http)(custom) TAR (of TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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