Low-dose bortezomib increases the expression of NKG2D and DNAM-1 ligands and enhances induced NK and γδ T cell-mediated lysis in multiple myeloma.
Low-dose bortezomib increases the expression of NKG2D and DNAM-1 ligands and enhances induced NK and γδ T cell-mediated lysis in multiple myeloma.
复制标题
低剂量硼替佐米可增加多发性骨髓瘤中 NKG2D 和 DNAM-1 配体的表达，并增强诱导的 NK 和 γ δ T 细胞介导的裂解
DOI：
10.18632/oncotarget.13979
复制
发表时间：
2017-01-24
期刊：
影响因子：
--
通讯作者：
Cui J
中科院分区：
文献类型：
--
作者：
Niu C;Jin H;Li M;Zhu S;Zhou L;Jin F;Zhou Y;Xu D;Xu J;Zhao L;Hao S;Li W;Cui J
多发性骨髓瘤（MM）是一种无法治愈的血液恶性肿瘤，尽管硼替佐米已显着改善其结果。越来越多的临床证据表明，增强用于输注的诱导的自然杀伤（NK）或γδ T细胞在MM的治疗中是有用的。然而，硼替佐米与诱导的NK和γδ T细胞的组合治疗是否进一步改善MM的结果，以及如何组合治疗，仍不清楚。在此，我们发现低剂量硼替佐米不抑制诱导的NK和γδ T细胞的活力，但诱导MM细胞凋亡。重要的是，低剂量硼替佐米增加了MM细胞上NKG 2D和DNAM-1配体的表达，这使多发性骨髓瘤细胞对诱导的NK和γδ T细胞的溶解敏感。我们的研究结果表明，低剂量硼替佐米和诱导的NK或γδ T细胞联合治疗对MM细胞具有协同的细胞毒作用。本研究为未来试验的设计和MM联合治疗策略的研究提供了原则证明。
Multiple myeloma (MM) is an incurable hematological malignancy, although bortezomib has markedly improved its outcomes. Growing clinical evidence indicates that enhancing induced natural killer (NK) or γδ T cells for infusion is useful in the treatment of MM. However, whether combination treatment with bortezomib and induced NK and γδ T cells further improves outcomes in MM, and how the treatments should be combined, remain unclear. Herein, we found that low-dose bortezomib did not suppress the viability of induced NK and γδ T cells, but did induce MM cell apoptosis. Importantly, low-dose bortezomib increased the expression of NKG2D and DNAM-1 ligands on MM cells, which sensitized the multiple myeloma cells to lysis by induced NK and γδ T cells. Our results suggested that combination treatment with low-dose bortezomib and induced NK or γδ T cells had a synergistic cytotoxic effect on MM cells. This study provided a proof of principle for the design of future trials and investigation of this combination therapeutic strategy for MM treatment.
DOI：
10.3760/cma.j.issn.0253-2727.2015.11.007
发表时间：
2015-11
影响因子：
--
作者：
Han W;Zhang X;Jia Z;He J;Chao H;Yang J;Xiao R;Lu X
通讯作者：
Lu X