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.

Détails

Ressource 1Télécharger: Wild 2015.pdf (553.70 [Ko])
Etat: Serval
Version: Author's accepted manuscript
ID Serval
serval:BIB_F776AF405398
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
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.
Périodique
Leukemia
Auteur(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
Statut éditorial
Publié
Date de publication
2015
Peer-reviewed
Oui
Volume
29
Numéro
8
Pages
1676-1683
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
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
Oui
Création de la notice
01/10/2015 15:36
Dernière modification de la notice
09/05/2019 3:38
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