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
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Chao Niu1,*, Haofan Jin1,*, Min Li1,*, Shan Zhu2, Lei Zhou1, Feng Jin1,3, Yulai Zhou3, Dongsheng Xu1, Jianting Xu1, Lianjing Zhao1, Shanshan Hao1,4, Wei Li1, Jiuwei Cui1
1Cancer Center, The First Hospital of Jilin University, Changchun 130021, China
2Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130021, China
3College of Pharmacy, Jilin University, Changchun 130021, China
4Department of Hematology, Taian Central Hospital, Taian 271000, China
*These authors contributed equally to this work as co-first authors
Wei Li, email: firstname.lastname@example.org
Jiuwei Cui, email: email@example.com
Keywords: bortezomib, multiple myeloma, natural killer cells, gamma-delta T cells
Received: September 24, 2016 Accepted: December 08, 2016 Published: December 16, 2016
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.
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