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

作者：Niu, Chao; Jin, Haofan; Li, Min; Zhu, Shan; Zhou, Lei; Jin, Feng; Zhou, Yulai; Xu, Dongsheng; Xu, Jianting; Zhao, Lianjing; Hao, Shanshan; Li, Wei^*; Cui, Jiuwei^*

来源：Oncotarget, 2017, 8(4): 5954-5964.

DOI：10.18632/oncotarget.13979

• bortezomib
• multiple myeloma
• natural killer cells
• gamma-delta T cells

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 gamma delta T cells for infusion is useful in the treatment of MM. However, whether combination treatment with bortezomib and induced NK and gamma delta 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 gamma delta 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 gamma delta T cells. Our results suggested that combination treatment with low-dose bortezomib and induced NK or gamma delta 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.

• 出版日期2017-1-24
• 单位吉林大学; 泰安市中心医院