Molecular action of lenalidomide in lymphocytes and hematologic malignancies.
Molecular action of lenalidomide in lymphocytes and hematologic malignancies.
复制标题
DOI：
10.1155/2012/513702
复制
发表时间：
2012
影响因子：
--
通讯作者：
Epling-Burnette PK
中科院分区：
文献类型：
--
作者：
McDaniel JM;Pinilla-Ibarz J;Epling-Burnette PK
免疫调节剂来那度胺是美国食品和药物管理局批准用于治疗骨髓增生异常综合征（MDS）和多发性骨髓瘤（MM）的沙利度胺的结构类似物。该药物目前也正在积极研究用于治疗慢性淋巴细胞白血病（CLL）和非霍奇金淋巴瘤（NHL），以及用于某些实体瘤和套细胞淋巴瘤（MCL）的药物组合。尽管来那度胺治疗已转化为MM和MDS总生存期的显著延长，并且相对于沙利度胺具有上级安全性和疗效，但其与免疫调节相关的作用机制仍不清楚。基于临床前模型和临床试验，来那度胺以及其他结构沙利度胺衍生物可增强T淋巴细胞的增殖和功能能力，并放大激活效应子反应和抑制炎症的共刺激信号传导途径。本文总结了我们目前对T细胞和自然杀伤（NK）细胞通路的理解，这些通路在造血系统肿瘤中被来那度胺修饰，为未来潜在的联合治疗决策提供信息。
The immunomodulatory agent, lenalidomide, is a structural analogue of thalidomide approved by the US Food and Drug Administration for the treatment of myelodysplastic syndrome (MDS) and multiple myeloma (MM). This agent is also currently under active investigation for the treatment of chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphoma (NHL), as well as in drug combinations for some solid tumors and mantle cell lymphoma (MCL). Although treatment with lenalidomide has translated into a significant extension in overall survival in MM and MDS and has superior safety and efficacy relative to thalidomide, the mechanism of action as it relates to immune modulation remains elusive. Based on preclinical models and clinical trials, lenalidomide, as well as other structural thalidomide derivatives, enhances the proliferative and functional capacity of T-lymphocytes and amplifies costimulatory signaling pathways that activate effector responses and suppress inflammation. This paper summarizes our current understanding of T- and natural killer (NK) cell pathways that are modified by lenalidomide in hematopoietic neoplasms to inform future decisions about potential combination therapies.