Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma.
Mechanism of action of immunomodulatory drugs (IMiDS) in multiple myeloma.
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DOI：
10.1038/leu.2009.236
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发表时间：
2010-01
期刊：
影响因子：
11.4
通讯作者：
Prince, H. M.
中科院分区：
文献类型：
--
作者：
Quach, H.;Ritchie, D.;Stewart, A. K.;Neeson, P.;Harrison, S.;Smyth, M. J.;Prince, H. M.
免疫调节药物（IMiDs）是沙利度胺类似物，具有免疫调节、抗血管生成、抗炎和抗增殖等多效抗骨髓瘤作用。他们的发展是促进了骨髓瘤（MM）生物学的理解，并开始了一个深刻的转变，在治疗方法对MM的IMiDs尽管在体外的各种影响，对他们的最终抗MM活性的相对贡献仍不清楚。基于体外数据，似乎抗增殖作用和关键细胞因子的下调是其最重要的抗MM属性。尽管对T和NK细胞的共刺激作用已被认为是IMiD增强抗MM免疫活性的独特且重要的特性，但这些体外作用尚未在体内得到确证。关于体内发生的免疫调节细胞因子的复杂相互作用，还有很多问题有待阐明，这最终决定了IMiDs在MM中的净效应-理解这一点对于促进这些药物在未来MM管理中的最佳操作是必要的。
Immunomodulatory drugs (IMiDs) are thalidomide analogues, which possess pleiotropic anti-myeloma properties including immune-modulation, anti-angiogenic, anti-inflammatory and anti-proliferative effects. Their development was facilitated by an improved understanding in myeloma (MM) biology and initiated a profound shift in the therapeutic approach towards MM. Despite the diverse effects of IMiDs in vitro, the relative contribution of each effect towards their ultimate anti-MM activity is still unclear. Based on in vitro data, it appears that anti-proliferative effects and downregulation of crucial cytokines are their most important anti-MM attributes. Although the co-stimulatory effects on T and NK cells have been heralded as a unique and important property of IMiDs towards enhancing anti-MM immune activity, these in vitro effects have yet to be firmly corroborated in vivo. Much is yet to be elucidated regarding the complex interplay of immunomodulatory cytokines that occurs in vivo, which ultimately dictates the net effects of IMiDs in MM—the understanding of which is necessary to facilitate optimal manipulation of these drugs in future MM management.
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