Institute of Pathology, University of Würzburg and Comprehensive Cancer Center (CCC) Mainfranken, Würzburg, Germany.
Institute of Pathology, University of Düsseldorf, Düsseldorf, Germany.
Cell Death Dis. 2018 Jan 24;9(2):86. doi: 10.1038/s41419-017-0157-6.
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.
耐药性是癌症治疗中的一个重大障碍，因此也是研究的一个常见主题。在套细胞淋巴瘤 (MCL) 患者中，已开发或原发性耐药限制了 B 细胞受体 (BCR) 途径抑制剂的治疗效果。最近的研究强调了核因子-κB (NFκB) 途径在 MCL 中对 BCR 抑制剂耐药中的作用。在这项研究中，我们分析了 MCL 细胞系对 NFκB 信号的依赖性，并说明了 CD40L 在 MCL 中激活替代 NFκB 途径的能力。这种激活导致对经典 NFκB 信号的不依赖，并导致对 BCR 抑制剂的耐药性。因此，配体（如 CD40L）及其对替代 NFκB 途径的激活对 MCL 中的药物反应有重大影响。此外，这项研究表明表达特定配体的细胞作为 MCL 细胞的微环境龛具有保护作用，并强调了在 MCL 中靶向替代 NFκB 信号的治疗意义。
