دورية
Lenalidomide enhances MOR202-dependent macrophage-mediated effector functions via the vitamin D pathway
| العنوان: | Lenalidomide enhances MOR202-dependent macrophage-mediated effector functions via the vitamin D pathway |
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| المؤلفون: | Busch, Leonhard, Mougiakakos, Dimitrios, Büttner-Herold, Maike, Müller, Miriam, Volmer, Dietrich, Bach, Christian, Fabri, Mario, Bittenbring, Jörg, Neumann, Frank, Boxhammer, Rainer, Nolting, Jens, Bisht, Savita, Böttcher, Martin, Jitschin, Simon, Hoffmann, Markus, Balzer, Heidi, Beier, Fabian, Gezer, Deniz, Dudziak, Diana, Gelse, Kolja, Hennig, Friedrich, Pallasch, Christian, Spriewald, Bernd, Mackensen, Andreas, Bruns, Heiko |
| المصدر: | Leukemia; November 2018, Vol. 32 Issue: 11 p2445-2458, 14p |
| مستخلص: | 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 increase the therapeutic efficacy of anti-CD38 antibodies such as MOR202, which remains to be investigated in clinical studies. |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 08876924 14765551 |
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| DOI: | 10.1038/s41375-018-0114-0 |