Lenalidomide enhances MOR202-dependent macrophage-mediated effector functions via the vitamin D pathway

Leukemia
Leonhard BuschHeiko Bruns

Abstract

Macrophages are key mediators of the therapeutic effects exerted by monoclonal antibodies, such as the anti-CD38 antibody MOR202, currently introduced in multiple myeloma (MM) therapy. Therefore, it is important to understand how antibody-mediated effector functions of myeloma-associated macrophages (MAMs) are regulated. Here, we focused on the effects of vitamin D, a known regulator of macrophage effector functions. Consequently, it was the aim of this study to assess whether modulation of the vitamin D pathway alters the tumoricidal activity of MAMs. Here, we demonstrate that MAMs display a defective vitamin D pathway with reduced expression level of CYP27B1 and limited tumoricidal activity which can be restored by the IMiD lenalidomide in vitro. Furthermore, our data indicate that the vitamin D pathway of MAMs from MM patients does recover during an IMiD-containing therapy shown by an improved MOR202-mediated cytotoxic activity of these MAMs against primary MM cells ex vivo. Here, the ex vivo cytotoxic activity could be further enhanced by vitamin D supplementation. These data suggest that vitamin D holds a key role for the effector functions of MAMs and that vitamin D supplementation in IMiD combination trials could further...Continue Reading

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Citations

Nov 8, 2018·The New England Journal of Medicine·Meletios A DimopoulosJesús San-Miguel
May 31, 2019·Clinical Reviews in Allergy & Immunology·Anne BordronYves Renaudineau
Aug 22, 2020·Expert Opinion on Investigational Drugs·Ying JiaoKongming Wu
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Sep 28, 2021·Blood Advances·Sushanth GouniPaolo Strati

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Datasets Mentioned

BETA
GM10861

Methods Mentioned

BETA
flow cytometry
FACS
biopsies
immunoprecipitation
ChIP
confocal microscopy
ChIP-Seq

Software Mentioned

Excel
GraphPad Prism

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