BET Inhibitor JQ1 Selectively Reduce Tregs by Upregulating STAT3 and Suppressing PD-1 Expression in Patients with Multiple Myeloma.
Adv Biol (Weinh)
; 8(7): e2300640, 2024 Jul.
Article
in En
| MEDLINE
| ID: mdl-38797917
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-ß1-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Azepines
/
Triazoles
/
T-Lymphocytes, Regulatory
/
STAT3 Transcription Factor
/
Programmed Cell Death 1 Receptor
/
Multiple Myeloma
Limits:
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Adv Biol (Weinh)
/
Advanced biology
Year:
2024
Document type:
Article
Country of publication:
Germany