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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Nov 11, 2020 |
| Title |
KRAS drives immune evasion in a genetic model of pancreatic cancer |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
We used CRISPR/Cas9 genome editing to inactivate KRAS in pancreatic cancer cells and isolated cell populations that still produce tumors in mice. We show that the malignant phenotype of KRAS knockout cells is stable. However, KRAS deficient cancer cells fail to avoid detection and elimination by the host immune system, indicating that a key aspect of tumor maintenance by oncogenic KRAS is to promote immune evasion. Our study uncovers changes both in cancer cells and stromal immunoreactive cells attributable to KRAS expression. Complementation studies indicate that BRAF, AKT and MYC are causative drivers of KRAS-mediated immune suppression. These results show that combination treatments that both target KRAS signaling and boost antitumor immunity will be an effective strategy to treat PDAC.
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| Overall design |
scRNAseq was performed on a total of three samples. Tumors were harvested from the pancreas of three sets of syngeneic mice. These mice were injected orthotopically with a) malignant KRASG12D p53R172H/+ b) KRASKO and c) KRAS KO BRAF/MYC cells.
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| Contributor(s) |
Ischenko I, D'Amico S, Rao M, Li J, Hayman MJ, Powers S, Petrenko O, Reich NC |
| Citation(s) |
33674596, 37732258, 38573819 |
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| Submission date |
Jun 11, 2019 |
| Last update date |
Apr 17, 2024 |
| Contact name |
Jinyu Li |
| E-mail(s) |
jinyu.li.1@stonybrook.edu
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| Organization name |
Stony Brook University
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| Department |
Cancer Center
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| Street address |
101 Nicolls Rd
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| City |
Stony Brook |
| State/province |
NY |
| ZIP/Postal code |
11794 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (3) |
| GSM3877995 |
Pancreatic tumors, KRAS G12D intact (scRNAseq) |
| GSM3877996 |
Pancreatic tumors, KRAS KO (scRNAseq) |
| GSM3877997 |
Pancreatic tumors, KRAS KO BRAF/MYC (scRNAseq) |
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| Relations |
| BioProject |
PRJNA548394 |
| SRA |
SRP201142 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE132582_RAW.tar |
205.1 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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