BET Inhibitor JQ1 Selectively Reduce Tregs by Upregulating STAT3 and Suppressing PD-1 Expression in Patients with

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.

Advanced Biology
|May 27, 2024
PubMed

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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