CD40L mediated alternative NFκB-signaling induces resistance to BCR-inhibitors in patients with mantle cell lymphoma
| Autor: | Hilka Rauert-Wunderlich, Andreas Rosenwald, Martina Rudelius, Ingolf Berberich |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer Research CD40 Ligand Immunology B-cell receptor Receptors Antigen B-Cell Context (language use) Lymphoma Mantle-Cell Article 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound immune system diseases Cell Line Tumor hemic and lymphatic diseases medicine Humans Bruton's tyrosine kinase ddc:610 lcsh:QH573-671 Tumor microenvironment biology Chemistry lcsh:Cytology NF-kappa B breakpoint cluster region Cell Biology medicine.disease Recombinant Proteins I-kappa B Kinase 030104 developmental biology Drug Resistance Neoplasm Ibrutinib biology.protein Cancer research Mantle cell lymphoma Signal transduction Signal Transduction |
| Zdroj: | Cell Death and Disease, Vol 9, Iss 2, Pp 1-9 (2018) Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-017-0157-6 |
| Popis: | 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 (NFκB) pathway in the context of resistance to BCR inhibitors in MCL. In this study, we analyzed the dependency of MCL cell lines on NFκB signaling and illustrated the ability of CD40L to activate the alternative NFκB pathway in MCL. This activation leads to independency of classical NFκB signaling and results in resistance to BCR inhibitors. Therefore, ligands (such as CD40L) and their activation of the alternative NFκB 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 NFκB signaling in MCL. |
| Databáze: | OpenAIRE |
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