Lenalidomide enhances MOR202-dependent macrophage-mediated effector functions via the vitamin D pathway
| Autor: | Simon Jitschin, Heiko Bruns, Leonhard Busch, Jens Nolting, Deniz Gezer, Rainer Boxhammer, Diana Dudziak, Bernd M. Spriewald, Christian P. Pallasch, Friedrich F. Hennig, Maike Büttner-Herold, Jörg Thomas Bittenbring, Dietrich A. Volmer, Frank Neumann, Andreas Mackensen, Markus H. Hoffmann, Christian Bach, Miriam J. Müller, Savita Bisht, Dimitrios Mougiakakos, Martin Böttcher, Heidi Balzer, Kolja Gelse, Mario Fabri, Fabian Beier |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research medicine.drug_class Regulator Monoclonal antibody 03 medical and health sciences 0302 clinical medicine Cell Line Tumor medicine Vitamin D and neurology Macrophage Cytotoxic T cell Humans Vitamin D Lenalidomide 25-Hydroxyvitamin D3 1-alpha-Hydroxylase Chemistry Cytotoxins Macrophages Antibodies Monoclonal Hematology ADP-ribosyl Cyclase 1 In vitro 030104 developmental biology Oncology Cell culture 030220 oncology & carcinogenesis Cancer research Multiple Myeloma Ex vivo |
| Zdroj: | Leukemia. 32(11) |
| ISSN: | 1476-5551 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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