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| Status |
Public on Aug 27, 2020 |
| Title |
ChIP-seq profiling of pancreatic tumor cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Compare epigentic features between WT and Kdm3a-KO tumor cells in two tumor cell lines (6419c5 and 6694c2) with two knockout tumor cell clones (KO1 and KO2). Although immunotherapy has revolutionized cancer care, patients with pancreatic ductal adenocarcinoma (PDA) rarely respond to these treatments, a failure that is attributed to poor infiltration and activation of T cells in the tumor microenvironment (TME). We performed an in vivo CRISPR screen and identified lysine demethylase 3A (KDM3A) as a potent epigenetic regulator of immunotherapy response in PDA. Mechanistically, KDM3A acts through Krueppel-like factor 5 (KLF5) and SMAD family member 4 (SMAD4) to regulate the expression of the epidermal growth factor receptor (EGFR). Ablation of KDM3A, KLF5, SMAD4, or EGFR in tumor cells altered the immune TME and sensitized tumors to combination immunotherapy, while treatment of established tumors with an EGFR inhibitor erlotinib prompted a dose-dependent increase in intratumoral T cells. This study defines an epigenetic-transcriptional mechanism by which tumor cells modulate their immune microenvironment and highlights the potential of EGFR inhibitors as immunotherapy sensitizers in PDA.
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| |
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| Overall design |
ChIP-seq analysis of WT and Kdm3a-KO 6419c5 and 6694c2 mouse pancreatic tumor cells
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| |
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| Contributor(s) |
Li J, Stanger B |
| Citation(s) |
33158848 |
| Submission date |
Aug 26, 2020 |
| Last update date |
Nov 26, 2020 |
| Contact name |
Jinyang Li |
| E-mail(s) |
jli05@rockefeller.edu
|
| Phone |
2155885072
|
| Organization name |
The Rockefeller University
|
| Lab |
Daniel Mucida Lab
|
| Street address |
1230 York Ave
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10065 |
| Country |
USA |
| |
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| Platforms (1) |
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| Samples (30)
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| Relations |
| BioProject |
PRJNA659482 |
| SRA |
SRP279024 |
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