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Updated: Dec 18, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

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Lenalidomide and pomalidomide potently interfere with induction of myeloid-derived suppressor cells in multiple

Saeko Kuwahara-Ota1, Yuji Shimura1, Christian Steinebach2

  • 1Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan.

British Journal of Haematology
|June 20, 2020
PubMed

Insights

Immunosuppressive myeloid-derived suppressor cells (MDSCs) drive multiple myeloma (MM) progression. Lenalidomide and pomalidomide inhibit MDSC induction by targeting myeloma cells and peripheral blood mononuclear cells, offering a novel therapeutic strategy.

Area of Science:

  • Immunology
  • Hematology
  • Cancer Biology

Background:

  • Increased immunosuppressive myeloid-derived suppressor cells (MDSCs) correlate with multiple myeloma (MM) progression and treatment resistance.
  • Understanding the mechanisms of MDSC induction is crucial for developing effective MM therapies.

Purpose of the Study:

  • To investigate the mechanisms by which myeloma cells induce MDSCs.
  • To identify strategies for preventing MDSC induction in MM.

Main Methods:

  • Utilized a transwell co-culture system with human myeloma-derived cell lines (HMCLs) and peripheral blood mononuclear cells (PBMCs).
  • Analyzed the role of C-C motif chemokine ligand 5 (CCL5) and macrophage migration inhibitory factor (MIF) in MDSC induction.
  • Evaluated the effects of immunomodulatory drugs (IMiDs) like lenalidomide (LEN) and pomalidomide (POM) on MDSC induction.

Main Results:

  • Four of nine HMCLs potently induced monocytic (M)-MDSCs from PBMCs.
  • Myeloma cell secretion of CCL5 and MIF was identified as a prerequisite for MDSC induction.
  • LEN and POM effectively inhibited MDSC induction by downregulating CCL5 and MIF in myeloma cells and affecting PBMCs.

Conclusions:

  • Myeloma-induced MDSCs are driven by CCL5 and MIF secretion.
  • LEN and POM inhibit MDSC induction through dual actions on myeloma cells and PBMCs.
  • These findings reveal a novel mechanism for IMiD efficacy in MM, targeting MDSC induction.
Keywords:
cereblonlenalidomidemultiple myelomamyeloid-derived suppressor cellpomalidomide

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