CD40L mediated alternative NF?B-signaling induces resistance to BCR-inhibitors in patients with mantle cell lymphoma.

ABSTRACT: Drug resistance is a significant obstacle in cancer treatment and therefore a frequent subject of research. Developed or primary resistance limits the treatment success of inhibitors of the B cell receptor (BCR) pathway in mantle cell lymphoma (MCL) patients. Recent research has highlighted the role of the nuclear factor-kappa B (NF?B) pathway in the context of resistance to BCR inhibitors in MCL. In this study, we analyzed the dependency of MCL cell lines on NF?B signaling and illustrated the ability of CD40L to activate the alternative NF?B pathway in MCL. This activation leads to independency of classical NF?B signaling and results in resistance to BCR inhibitors. Therefore, ligands (such as CD40L) and their activation of the alternative NF?B pathway have a major impact on the drug response in MCL. Furthermore, this study indicates a protective role for cells expressing specific ligands as microenvironmental niches for MCL cells and underlines the significance of therapeutically targeting alternative NF?B signaling in MCL.

SUBMITTER: Rauert-Wunderlich H 

PROVIDER: S-EPMC5833745 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature