细胞因子诱导的杀伤细胞
癌症研究
NKG2D公司
多发性骨髓瘤
丁酸钠
细胞毒性
免疫疗法
细胞因子
活力测定
细胞培养
细胞
化学
免疫系统
免疫学
生物
CD8型
体外
生物化学
CD3型
遗传学
作者
Chidimma A. Nwangwu,Hans Weiher,Amit Sharma
摘要
Multiple myeloma, which is a monoclonal plasma cell malignancy, still remains incurable despite recent progress in our understanding of this disorder. Adoptive immunotherapy of multiple myeloma using cytokine-induced killer cells is yielding promising results in clinical trials; however, some myeloma cells still evade immune surveillance by various unknown molecular mechanisms. This study aims at increasing the efficacy of cytokine-induced killer cells in targeting this tumor, using selective small-molecule inhibitors which increase and stabilize surface expression of the natural killer group 2, member D ligand, major histocompatibility complex class I polypeptide-related sequence A (MICA) on myeloma cells. We treated 2 multiple myeloma cell lines-U266 and KMS-12-PE-with 3 drugs. One of these drugs (sodium butyrate) is a histone deacetylase inhibitor. Another drug which was used (matrix metalloproteinase inhibitor III) blocks ligand shedding while the third drug (phenylarsine oxide) obstructs surface ligand internalization. The effect of these drugs on cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, surface ligand expression was examined using flow cytometry, and ligand shedding was assessed using enzyme-linked immunosorbent assay. We demonstrated that cytokine-induced killer cells have increased cytotoxicity against multiple myeloma cells after combined drug treatment than without drug pretreatment. We also established that this increased cytotoxicity was due to potent upregulation and stabilization of surface MICA on the surface of these tumor cell lines. Our study thus highlights further therapeutic options which could be used for the treatment of multiple myeloma patients.
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