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

Busch L, Mougiakakos D, Büttner-Herold M, Müller MJ, Volmer DA, Bach C, Fabri M, Bittenbring JT, Neumann F, Boxhammer R, Nolting J, Bisht S, Böttcher M, Jitschin S, Hoffmann M, Balzer H, Beier F, Gezer D, Dudziak D, Gelse K, Hennig F, Pallasch CP, Spriewald B, Mackensen A, Bruns H (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Leukemia Springer Nature

DOI: 10.1038/s41375-018-0114-0

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 increase the therapeutic efficacy of anti-CD38 antibodies such as MOR202, which remains to be investigated in clinical studies.

Authors with CRIS profile

Dimitrios Mougiakakos Professur für Hämatologie/Onkologie mit dem Schwerpunkt Tumorimmunologie Maike Büttner-Herold Department of Nephropathology Christian Bach Department of Medicine 5 – Haematology and Oncology Martin Böttcher Department of Medicine 5 – Haematology and Oncology Markus Hoffmann Department of Medicine 3 – Rheumatology and Immunology Diana Dudziak Professur für die Biologie Dendritischer Zellen Friedrich Hennig Unfallchirurgische Abteilung in der Chirurgischen Klinik Andreas Mackensen Lehrstuhl für Innere Medizin V Heiko Bruns Department of Medicine 5 – Haematology and Oncology

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Universität des Saarlandes (UdS) DE Germany (DE) Universitätsklinikum des Saarlandes (UKS) DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE) MorphoSys AG DE Germany (DE) Universitätsklinikum Aachen (UKA) DE Germany (DE) Universität zu Köln DE Germany (DE) Universitätsklinikum Köln DE Germany (DE)

How to cite

APA:

Busch, L., Mougiakakos, D., Büttner-Herold, M., Müller, M.J., Volmer, D.A., Bach, C.,... Bruns, H. (2018). Lenalidomide enhances MOR202-dependent macrophage-mediated effector functions via the vitamin D pathway. Leukemia. https://doi.org/10.1038/s41375-018-0114-0

MLA:

Busch, Leonhard, et al. "Lenalidomide enhances MOR202-dependent macrophage-mediated effector functions via the vitamin D pathway." Leukemia (2018).

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