PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Bruns, H.* ; Büttner, M.* ; Fabri, M.* ; Mougiakakos, D.* ; Bittenbring, J.T.* ; Hoffmann, M.H.* ; Beier, F.* ; Pasemann, S.* ; Jitschin, R.* ; Hofmann, A.D.* ; Neumann, F.J.* ; Daniel, C.* ; Maurberger, A.* ; Kempkes, B. ; Amann, K.* ; Mackensen, A.* ; Gerbitz, A.*

Vitamin D-dependent induction of cathelicidin in human macrophages results in cytotoxicity against high-grade B cell lymphoma.

Sci. Transl. Med. 7:282ra47 (2015)
Publ. Version/Full Text DOI PMC
Closed
Open Access Green as soon as Postprint is submitted to ZB.
Infiltration by macrophages represents a characteristic morphological hallmark in high-grade lymphatic malignancies such as Burkitt's lymphoma (BL). Although macrophages can, in principle, target neoplastic cells and mediate antibody-dependent cellular cytotoxicity (ADCC), tumor-associated macrophages (TAMs) regularly fail to exert direct cytotoxic functions. The underlying mechanisms responsible for this observation remain unclear. We demonstrate that inflammatory M1 macrophages kill proliferating high-grade B cell lymphoma cells by releasing the antimicrobial peptide cathelicidin in a vitamin D-dependent fashion. We show that cathelicidin directly induces cell death by targeting mitochondria of BL cells. In contrast, anti-inflammatory M2 macrophages and M2-like TAMs in BL exhibit an altered vitamin D metabolism, resulting in a reduced production of cathelicidin and consequently in inability to lyse BL cells. However, treatment of M2 macrophages with the bioactive form of vitamin D, 1,25D3, or a vitamin D receptor agonist effectively induces cathelicidin production and triggers tumoricidal activity against BL cells. Furthermore, rituximab-mediated cytotoxicity of vitamin D-treated M2 macrophages is cathelicidin-dependent. Finally, vitamin D treatment of 25-hydroxyvitamin D (25D)-deficient volunteers in vivo or primary TAMs in vitro improves rituximab-mediated ADCC against B cell lymphoma cells. These data indicate that activation of the vitamin D signaling pathway activates antitumor activity of TAMs and improves the efficacy of ADCC.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Scopus
Cited By
Altmetric
15.843
2.941
32
49
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Antimicrobial Peptide Ll-37; Non-hodgkins-lymphoma; Tumor-associated Macrophages; Bacillus-calmette-guerin; Human-monocytes; Monoclonal-antibody; Cancer Progression; Innate Immunity; D-receptor; Rituximab
Language english
Publication Year 2015
HGF-reported in Year 2015
ISSN (print) / ISBN 1946-6234
e-ISSN 1946-6242
Journal Science Translational Medicine
Quellenangaben Volume: 7, Issue: 282, Pages: , Article Number: 282ra47 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington
Reviewing status Peer reviewed
Institute(s) Research Unit Gene Vector (AGV)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Immune Response and Infection
PSP Element(s) G-501500-002
PubMed ID 25855493
DOI 10.1126/scitranslmed.aaa3230
WOS ID WOS:000352535200004
Scopus ID 84927587443
Erfassungsdatum 2015-04-11
[➜Report correction]