BET Inhibitor Exposure Impacts on Cancer Cells’ Surface Expression of NK Cell Ligands
Presenter Type
UNO Undergraduate Student
Major/Field of Study
Biology
Other
Biology
Advisor Information
Dr. Paul W Denton
Location
CEC RM #231
Presentation Type
Oral Presentation
Start Date
22-3-2024 1:00 PM
End Date
22-3-2024 2:15 PM
Abstract
BET Inhibitor Exposure Impacts on Cancer Cells’ Surface Expression of NK Cell Ligands
Nathan Booher1, Audrey L. Smith2, Dalia El-Gamal, PhD2, Paul W. Denton, PhD1
1Department of Biology, University of Nebraska at Omaha
2Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center
The primary objective of our collaboration is to improve the killing of diseased (target) cells by human natural killer (NK) cells. Herein, we are asking how a BET inhibitor directly impacts target cells. BET inhibitors are a class of anti-cancer drugs that interfere with BET proteins’ roles in transcription and cell cycle regulation. We hypothesize that BET inhibition will change target cells’ expression of surface proteins that interact with NK cells – an outcome which could influence NK cell-mediated killing of the targets. Relevant surface proteins to measure on targets include: MICA/B, HLA-E, and CD20. The surface ligand MICA/B (an MHC associated protein) interacts with NK cell receptor NKG2D. Additionally, HLA-E (an MHC class I molecule) inhibits NK cell lysis. Finally, CD20, a surface ligand on our B-cell lymphoma cells, plays an integral role in mediating antibody dependent cellular cytotoxicity. For these experiments, Daudi (B-cell lymphoma) and K562 (leukemia) target cell lines are exposed to a BET inhibitor. Target cells are then stained with fluorophore-conjugated antibodies specific for each ligand. At this point, ligand-expression levels for each marker are determined via flow cytometry. We expect that data collected through these experiments will provide valuable insights into the clinical potential for BET inhibitors to modulate NK cell killing outcomes. Results to date will be presented.
BET Inhibitor Exposure Impacts on Cancer Cells’ Surface Expression of NK Cell Ligands
CEC RM #231
BET Inhibitor Exposure Impacts on Cancer Cells’ Surface Expression of NK Cell Ligands
Nathan Booher1, Audrey L. Smith2, Dalia El-Gamal, PhD2, Paul W. Denton, PhD1
1Department of Biology, University of Nebraska at Omaha
2Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center
The primary objective of our collaboration is to improve the killing of diseased (target) cells by human natural killer (NK) cells. Herein, we are asking how a BET inhibitor directly impacts target cells. BET inhibitors are a class of anti-cancer drugs that interfere with BET proteins’ roles in transcription and cell cycle regulation. We hypothesize that BET inhibition will change target cells’ expression of surface proteins that interact with NK cells – an outcome which could influence NK cell-mediated killing of the targets. Relevant surface proteins to measure on targets include: MICA/B, HLA-E, and CD20. The surface ligand MICA/B (an MHC associated protein) interacts with NK cell receptor NKG2D. Additionally, HLA-E (an MHC class I molecule) inhibits NK cell lysis. Finally, CD20, a surface ligand on our B-cell lymphoma cells, plays an integral role in mediating antibody dependent cellular cytotoxicity. For these experiments, Daudi (B-cell lymphoma) and K562 (leukemia) target cell lines are exposed to a BET inhibitor. Target cells are then stained with fluorophore-conjugated antibodies specific for each ligand. At this point, ligand-expression levels for each marker are determined via flow cytometry. We expect that data collected through these experiments will provide valuable insights into the clinical potential for BET inhibitors to modulate NK cell killing outcomes. Results to date will be presented.