Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.

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Ressource 1Download: Wild 2015.pdf (553.70 [Ko])
State: Public
Version: Author's accepted manuscript
Serval ID
serval:BIB_F776AF405398
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.
Journal
Leukemia
Author(s)
Wild J., Schmiedel B.J., Maurer A., Raab S., Prokop L., Stevanović S., Dörfel D., Schneider P., Salih H.R.
ISSN
1476-5551 (Electronic)
ISSN-L
0887-6924
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
29
Number
8
Pages
1676-1683
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Natural killer (NK) cells are cytotoxic lymphocytes that substantially contribute to the therapeutic benefit of antitumor antibodies like Rituximab, a crucial component in the treatment of B-cell malignancies. In chronic lymphocytic leukemia (CLL), the ability of NK cells to lyse the malignant cells and to mediate antibody-dependent cellular cytotoxicity upon Fc receptor stimulation is compromised, but the underlying mechanisms are largely unclear. We report here that NK-cells activation-dependently produce the tumor necrosis factor family member 'B-cell activating factor' (BAFF) in soluble form with no detectable surface expression, also in response to Fc receptor triggering by therapeutic CD20-antibodies. BAFF in turn enhanced the metabolic activity of primary CLL cells and impaired direct and Rituximab-induced lysis of CLL cells without affecting NK reactivity per se. The neutralizing BAFF antibody Belimumab, which is approved for treatment of systemic lupus erythematosus, prevented the effects of BAFF on the metabolism of CLL cells and restored their susceptibility to direct and Rituximab-induced NK-cell killing in allogeneic and autologous experimental systems. Our findings unravel the involvement of BAFF in the resistance of CLL cells to NK-cell antitumor immunity and Rituximab treatment and point to a benefit of combinatory approaches employing BAFF-neutralizing drugs in B-cell malignancies.
Pubmed
Web of science
Open Access
Yes
Create date
01/10/2015 14:36
Last modification date
20/08/2019 16:23
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