Busch, Leonhard, Mougiakakos, Dimitrios, Buettner-Herold, Maike, Mueller, Miriam J., Volmer, Dietrich A., Bach, Christian ORCID: 0000-0003-4675-7896, Fabri, Mario, Bittenbring, Joerg T., Neumann, Frank, Boxhammer, Rainer, Nolting, Jens, Bisht, Savita, Boettcher, Martin, Jitschin, Simon, Hoffmann, Markus H., Balzer, Heidi, Beier, Fabian ORCID: 0000-0002-3718-8217, Gezer, Deniz, Dudziak, Diana, Gelse, Kolja, Hennig, Friedrich F., Pallasch, Christian P. ORCID: 0000-0001-5675-6905, Spriewald, Bernd, Mackensen, Andreas and Bruns, Heiko (2018). Lenalidomide enhances MOR202-dependent macrophage -mediated effector functions via the vitamin D pathway. Leukemia, 32 (11). S. 2445 - 2459. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-5551

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Busch, LeonhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mougiakakos, DimitriosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner-Herold, MaikeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, Miriam J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Volmer, Dietrich A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bach, ChristianUNSPECIFIEDorcid.org/0000-0003-4675-7896UNSPECIFIED
Fabri, MarioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bittenbring, Joerg T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neumann, FrankUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boxhammer, RainerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nolting, JensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bisht, SavitaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boettcher, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jitschin, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hoffmann, Markus H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Balzer, HeidiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beier, FabianUNSPECIFIEDorcid.org/0000-0002-3718-8217UNSPECIFIED
Gezer, DenizUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dudziak, DianaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gelse, KoljaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hennig, Friedrich F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pallasch, Christian P.UNSPECIFIEDorcid.org/0000-0001-5675-6905UNSPECIFIED
Spriewald, BerndUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mackensen, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruns, HeikoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-167919
DOI: 10.1038/s41375-018-0114-0
Journal or Publication Title: Leukemia
Volume: 32
Number: 11
Page Range: S. 2445 - 2459
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 1476-5551
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TUMOR-ASSOCIATED MACROPHAGES; MULTIPLE-MYELOMA CELLS; CD38 GENE-EXPRESSION; TRANS-RETINOIC ACID; FOLLICULAR LYMPHOMA; UP-REGULATION; D DEFICIENCY; CELLULAR CYTOTOXICITY; B-CELLS; DEXAMETHASONEMultiple languages
Oncology; HematologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/16791

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