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Series GSE225170 Query DataSets for GSE225170
Status Public on Feb 17, 2023
Title scRNA-seq of cancer and CD8+ cells during early metastasis identifies targetable subpopulations and immune evasion mechanisms
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Profiling tumors at single-cell resolution provides an opportunity to understand complexities underpinning lymph-node metastases in head and neck squamous-cell carcinoma. Single-cell RNAseq (scRNAseq) analysis of cancer-cell trajectories identifies a sub-population of pre-metastatic cells, driven by actionable pathways including AXL and AURK. Blocking these two proteins blunts tumor invasion in patient-derived cultures. Furthermore, scRNAseq analyses of tumor-infiltrating CD8+ T-lymphocytes show two distinct trajectories to T-cell dysfunction, corroborated by their clonal architecture based on single-cell T-cell receptor sequencing. By determining key modulators of these trajectories, followed by validation using external datasets and functional experiments, we uncover a role for SOX4 in mediating T-cell exhaustion. Finally, interactome-analyses between pre-metastatic tumor-cells and CD8+ T-lymphocytes uncover a putative role for the Midkine pathway in immune-modulation and this is confirmed by scRNAseq of tumors from humanized mice. Aside from specific findings, this study demonstrates the importance of tumor heterogeneity analyses in identifying key vulnerabilities during early metastasis.
 
Overall design Examining the tumor microenvironment of humanized mouse model of head and neck squamous cell cancer (HNSCC) treated with Pembrolizumab (anti-PD1)
 
Contributor(s) Quah HS, Cao EY, Iyer NG
Citation(s) 36973261
Submission date Feb 13, 2023
Last update date May 26, 2023
Contact name Yiqun Elaine Cao
Organization name Duke-NUS Medical School
Street address 8 College Road
City Singapore
ZIP/Postal code 169857
Country Singapore
 
Platforms (1)
GPL21103 Illumina HiSeq 4000 (Mus musculus)
Samples (2)
GSM7040719 Control, NOG-EXL, scRNAseq
GSM7040720 Anti-PD1, NOG-EXL, scRNAseq
Relations
BioProject PRJNA934286
SRA SRP422246

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE225170_CTRLPD1_final.rds.gz 1.2 Gb (ftp)(http) RDS
GSE225170_RAW.tar 107.0 Mb (http)(custom) TAR (of MTX, TSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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