BET Inhibitor JQ1 Selectively Reduce Tregs by Upregulating STAT3 and Suppressing PD-1 Expression in Patients with Multiple Myeloma
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Updated: Jun 25, 2025

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
Youxue Huang1, Mengjun Zhong1,2, Rili Gao3
1Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, 510632, P. R. China.
Abstract:
Multiple myeloma (MM) stands as a prevalent hematological malignancy, primarily incurable, originating from plasma cell clones. MM's progression encompasses genetic abnormalities and disruptions in the bone marrow microenvironment, leading to tumor proliferation, immune dysfunction, and compromised treatment outcomes. Emerging evidence highlights the critical role of regulatory T cells (Tregs) in MM progression, suggesting that targeting Tregs could enhance immune functionality and treatment efficacy. In this study, a notable increase in Treg proportions within MM patients' bone marrow (BM) compared to healthy individuals is observed. Additionally, it is found that the bromodomain and extraterminal domain (BET) inhibitor JQ1 selectively diminishes Treg percentages in MM patients' BM and reduces TGF-β1-induced Tregs. This reduction occurs via inhibiting cell viability and promoting apoptosis. RNA sequencing further indicates that JQ1's inhibitory impact on Tregs likely involves upregulating STAT3 and suppressing PD-1 expression. Collectively, these findings suggest JQ1's potential to modulate Tregs, bolstering the immune response in MM and introducing a promising avenue for MM immunotherapy.
Insights
Regulatory T cells (Tregs) increase in multiple myeloma (MM). The BET inhibitor JQ1 reduces Tregs in MM patients by promoting apoptosis, suggesting potential for novel immunotherapy.
Area of Science:
- Hematological Oncology
- Immunology
- Cancer Biology
Background:
- Multiple myeloma (MM) is an incurable plasma cell malignancy.
- MM progression involves genetic changes and bone marrow microenvironment disruption, leading to immune dysfunction.
- Regulatory T cells (Tregs) play a critical role in MM progression and immune evasion.
Purpose of the Study:
- To investigate the role of Tregs in MM.
- To evaluate the effect of the BET inhibitor JQ1 on Tregs in MM.
Main Methods:
- Quantification of Treg proportions in bone marrow (BM) of MM patients and healthy individuals.
- Assessment of JQ1's effect on Treg percentages and TGF-β1-induced Tregs.
- RNA sequencing to elucidate JQ1's molecular mechanisms.
Main Results:
- Treg proportions were significantly increased in MM patients' BM compared to healthy controls.
- JQ1 selectively reduced Treg percentages in MM patients' BM and inhibited TGF-β1-induced Tregs.
- JQ1 reduced Treg viability and induced apoptosis, likely via STAT3 upregulation and PD-1 downregulation.
Conclusions:
- JQ1 demonstrates potential in modulating Tregs within the MM bone marrow microenvironment.
- Targeting Tregs with JQ1 may enhance anti-tumor immune responses in MM.
- These findings support JQ1 as a promising candidate for MM immunotherapy development.
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