Presenter Status
Fellow
Abstract Type
Research
Primary Mentor
John Perry
Start Date
13-5-2021 11:30 AM
End Date
13-5-2021 1:30 PM
Presentation Type
Poster Presentation
Description
Background: Evasion of drug and immune response in therapy-resistant leukemic stem cells (LSCs) is a major cause of relapse. A previous study has identified an alternative mechanism of action for low-dose doxorubicin (DXR) that inhibits upregulation of immune checkpoints (IC) in LSCs.
Objectives/Goal: The objective of this study is to establish the DXR dose range that will achieve the inhibition of immune checkpoint expression in leukemic cell lines.
Methods/Design: Cells were analyzed for expression of CTLA-4, LAG-3, PD-1, TIGIT, and TIM-3 via flow cytometry. Analysis was performed on days 3, 5, and 8 of treatment at concentrations identified as low, intermediate, and high from previously generated kill curve data.
Results: These results show that low dose DXR inhibits upregulation of multiple ICs within the first few days of treatment. Follow up study will be necessary for replication, with particular focus on measuring IC expression within the first three days of treatment.
Conclusions: Overall, this presents a promising strategy for treating resistant LSCs using an established chemotherapeutic agent.
MeSH Keywords
Hematological disease; chemotherapy; neoplasms
Included in
Higher Education and Teaching Commons, Medical Education Commons, Neoplasms Commons, Pediatrics Commons, Science and Mathematics Education Commons
Low Dose Doxorubicin Inhibits Immune Checkpoint Upregulation in Acute Leukemias
Background: Evasion of drug and immune response in therapy-resistant leukemic stem cells (LSCs) is a major cause of relapse. A previous study has identified an alternative mechanism of action for low-dose doxorubicin (DXR) that inhibits upregulation of immune checkpoints (IC) in LSCs.
Objectives/Goal: The objective of this study is to establish the DXR dose range that will achieve the inhibition of immune checkpoint expression in leukemic cell lines.
Methods/Design: Cells were analyzed for expression of CTLA-4, LAG-3, PD-1, TIGIT, and TIM-3 via flow cytometry. Analysis was performed on days 3, 5, and 8 of treatment at concentrations identified as low, intermediate, and high from previously generated kill curve data.
Results: These results show that low dose DXR inhibits upregulation of multiple ICs within the first few days of treatment. Follow up study will be necessary for replication, with particular focus on measuring IC expression within the first three days of treatment.
Conclusions: Overall, this presents a promising strategy for treating resistant LSCs using an established chemotherapeutic agent.
Comments
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