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Series GSE262027 Query DataSets for GSE262027
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
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.
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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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
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
Platforms (1)
GPL34315 nCounter PanCancer IO 360 Panel
Samples (12)
GSM8156208 Spleen_VEH_1
GSM8156209 Spleen_VEH_2
GSM8156210 Spleen_VEH_3
BioProject PRJNA1090059

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE262027_RAW.tar 110.0 Kb (http)(custom) TAR (of RCC)
Raw data provided as supplementary file
Processed data included within Sample table

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