The immunomodulatory-drug, lenalidomide, sustains and enhances interferon-α production by human plasmacytoid dendritic cells

Journal of Blood Medicine
Kayoko KibataShosaku Nomura

Abstract

Background: Lenalidomide (LEN), an immunomodulatory drug (IMiD), is currently used for treatment of multiple myeloma (MM). LEN potentiates T cell and natural killer cell functions. However, the cellular and molecular mechanisms underlying the immunomodulatory effects of LEN remain unclear. We focused on the effects of LEN on human plasmacytoid dendritic cells (pDCs), which are the major source of interferon (IFN)-α in the blood and play a central role in innate immune responses. Results: We found that bortezomib, a proteasome inhibitor used to treat MM, killed pDCs but that 0.1-3 μM LEN (covering clinical plasma concentration range) did not affect pDC survival or CD86 expression. Bortezomib inhibited pDC-derived IFN-α production in a dose-dependent fashion, but 0.1-3 µM LEN sustained pDC-derived IFN-α production when stimulated with an optimal concentration of CpG-ODN 2216 (3 μM). In pDCs stimulated with a low concentration of CpG-ODN (0.1 μM), LEN enhanced IFN-α production. These results indicated that LEN, when used at a clinically relevant concentration, can potentially enhance IFN-α production by pDCs. Conclusion: Collectively, our findings unveiled a novel target of LEN and extend the repertoire of the drug's known immunom...Continue Reading

Citations

Nov 23, 2019·Cancers·Yutaka TsukuneNorio Komatsu
Jan 24, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Kanchan YadavRenu Tripathi

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Methods Mentioned

BETA
flow cytometry
ELISA

Software Mentioned

GraphPad Prism
GraphPad

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