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

Autor: Busch L; Department of Internal Medicine 5-Hematology/Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Mougiakakos D; Department of Internal Medicine 5-Hematology/Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Büttner-Herold M; Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Müller MJ; Institute of Bioanalytical Chemistry, Saarland University, Saarbrücken, Germany., Volmer DA; Institute of Bioanalytical Chemistry, Saarland University, Saarbrücken, Germany., Bach C; Department of Internal Medicine 5-Hematology/Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Fabri M; Department of Dermatology, University of Cologne, Cologne, Germany., Bittenbring JT; Medizinische Klinik I, Saarland University Medical School, Homburg/Saar, Germany., Neumann F; Medizinische Klinik I, Saarland University Medical School, Homburg/Saar, Germany., Boxhammer R; MorphoSys AG, Planegg, Germany., Nolting J; Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany., Bisht S; Department of Oncology, Hematology and Rheumatology, University Hospital Bonn, Bonn, Germany., Böttcher M; Department of Internal Medicine 5-Hematology/Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Jitschin S; Department of Internal Medicine 5-Hematology/Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Hoffmann MH; Department of Internal Medicine 3, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Balzer H; Department of Internal Medicine 5-Hematology/Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Beier F; Department of Oncology, Hematology and Stem Cell Transplantation, RWTH Medical School, Aachen, Germany., Gezer D; Department of Oncology, Hematology and Stem Cell Transplantation, RWTH Medical School, Aachen, Germany., Dudziak D; Department of Dermatology, Laboratory of Dendritic Cell Biology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Gelse K; Department of Trauma Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Hennig FF; Department of Trauma Surgery, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Pallasch CP; Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany., Spriewald B; Department of Internal Medicine 5-Hematology/Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Mackensen A; Department of Internal Medicine 5-Hematology/Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany., Bruns H; Department of Internal Medicine 5-Hematology/Oncology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), Erlangen, Germany. heiko.bruns@uk-erlangen.de.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2018 Nov; Vol. 32 (11), pp. 2445-2458. Date of Electronic Publication: 2018 Mar 28.
DOI: 10.1038/s41375-018-0114-0
Abstrakt: 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: MEDLINE
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