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GEO help: Mouse over screen elements for information. |
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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
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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.
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Overall design |
Examining the tumor microenvironment of humanized mouse model of head and neck squamous cell cancer (HNSCC) treated with Pembrolizumab (anti-PD1)
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Contributor(s) |
Quah HS, Cao EY, Iyer NG |
Citation(s) |
36973261 |
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Submission date |
Feb 13, 2023 |
Last update date |
May 26, 2023 |
Contact name |
Yiqun Elaine Cao |
Organization name |
Duke-NUS Medical School
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Street address |
8 College Road
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City |
Singapore |
ZIP/Postal code |
169857 |
Country |
Singapore |
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Platforms (1) |
GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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Samples (2) |
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Relations |
BioProject |
PRJNA934286 |
SRA |
SRP422246 |
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 Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
Processed data are available on Series record |
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