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| Status |
Public on Mar 01, 2024 |
| Title |
Comparative Transcriptomic Analysis of aKO and p-aKO in Pancreatic Cancer Cells |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Most human pancreatic ductal adenocarcinoma (PDAC) are not infiltrated with cytotoxic T cells and are highly resistant to immunotherapy. Over 90% of PDAC have oncogenic KRAS mutations, and phosphoinositide 3-kinases (PI3Ks) are direct effectors of KRAS. Our previous study demonstrated that ablation of Pik3ca in KPC (KrasG12D; Trp53R172H; Pdx1-Cre) pancreatic cancer cells induced host T cells to infiltrate and completely eliminate the tumors in a syngeneic orthotopic implantation mouse model. This study now shows that implantation of Pik3ca-/- KPC (named αKO) cancer cells induces clonal expansion of cytotoxic T cells infiltrating the pancreatic tumors in this mouse model. To identify potential molecules that can regulate the activity of these anti-tumor T cells, we conducted an in vivo genome-wide gene-deletion screen using αKO cells implanted in the mouse pancreas. The result shows that deletion of propionyl-CoA carboxylase subunit B gene (Pccb) in αKO cells (named p-αKO) leads to immune evasion, tumor progression and death of host mice. Surprisingly, p-αKO tumors are still infiltrated with T cells but they are inactive against tumor cells. However, blockade of PD-L1/PD1 interaction reactivated clonally expanded T cells infiltrating p-αKO tumors, leading slower tumor progression and improve survival of host mice. These results indicate that Pccb can modulate the activity of cytotoxic T cells infiltrating some pancreatic tumors and this understanding may help to improve immunotherapy for PDAC.
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| Overall design |
aKO cells were generated by knocking out p110a from KPC, and Pccb was knocked out from aKO cells and generated p-aKO cells. Total RNA was extracted from the two cell lines (aKO vs p-aKO) and after polyA enrichment and library prep, samples were sequenced by illumina PE150.
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| Contributor(s) |
Han H, Lin R |
| Citation missing |
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| BioProject |
PRJNA1068768 |
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| Submission date |
Jan 26, 2024 |
| Last update date |
Mar 02, 2024 |
| Contact name |
Richard Lin |
| E-mail(s) |
Richard.Lin@stonybrook.edu
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| Organization name |
Stony Brook University
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| Street address |
1 Circle Road
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| City |
Stony Brook |
| ZIP/Postal code |
11790 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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