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| Status |
Public on May 21, 2024 |
| Title |
BET inhibition reforms the immune microenvironment and alleviates T-cell dysfunction in chronic lymphocytic leukemia |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Redundant tumor microenvironment (TME) immunosuppressive mechanisms and epigenetic maintenance of terminal T-cell exhaustion greatly hinder functional anti-tumor T-cell responses in chronic lymphocytic leukemia (CLL). Bromodomain and extra-terminal (BET) proteins regulate key pathways contributing to CLL pathogenesis and TME interactions, including T-cell function and differentiation. Herein, we report that blocking BET protein function alleviates immunosuppressive networks in the CLL TME and repairs inherent T-cell defects. The pan-BET inhibitor OPN-51107 reduced exhaustion-associated cell signatures, fostering improved T-cell proliferation and effector function in patient samples and murine models of CLL. These findings establish the immunomodulatory action of BET-i on CLL T-cells and support the use of BET inhibitors in treatment strategies for CLL.
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| Overall design |
In order to assay the global effect of the BET inhibitor OPN-51107 on the chronic lymphocytic leukemia tumor microenvironment, Eμ-TCL1 adoptive transfer mice were treated with OPN-51107 or vehicle control for 3 weeks. Murine splenic cells and peripheral blood mononuclear cells (PBMCs) were then evaluated for gene expression changes using the NanoString PanCancer IO 360™ Panel.
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/38775157/
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| Contributor(s) |
Smith AL, Skupa SA, Eiken AP, Reznicek TE, Schmitz E, Williams N, Moore DY, D'Angelo CR, Kallam A, Lunning MA, Bociek RG, Vose JM, Mohamed E, Mahr AR, Denton PW, Powell B, Bollag G, Rowley MJ, El-Gamal D |
| Citation(s) |
38775157 |
| |
| Submission date |
Mar 20, 2024 |
| Last update date |
May 22, 2024 |
| Contact name |
Dalia El-Gamal |
| E-mail(s) |
[email protected]
|
| Phone |
4025595241
|
| Organization name |
University of Nebraska Medical Center
|
| Department |
Eppley Institute
|
| Street address |
986805 NE Med Center BCC 4.12.396
|
| City |
Omaha |
| State/province |
NE |
| ZIP/Postal code |
68198-6805 |
| Country |
USA |
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| Platforms (1) |
| GPL34315 |
nCounter PanCancer IO 360 Panel |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA1090059 |
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