Checkpoint inhibition in myeloma
Checkpoint inhibition in myeloma
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DOI：
10.1182/asheducation-2016.1.528
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发表时间：
2016-12-01
影响因子：
3
通讯作者：
Benson, Don M., Jr.
中科院分区：
文献类型：
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作者：
Benson, Don M., Jr.
从历史上看，癌症免疫疗法的尝试都强调旨在刺激或增强免疫系统发挥作用的策略。在过去的十年中，开发了一种补充方法，即将免疫细胞从抑制性束缚中释放出来。关于免疫如何调节、免疫系统如何与恶性肿瘤相互作用以及癌细胞如何利用这些过程逃避检测等基础生物学的发现，都已转化为快速发展的癌症免疫检查点抑制治疗领域。骨髓瘤是一种与严重免疫功能障碍相关的恶性肿瘤，该功能障碍是由疾病本身以及过去使用的许多免疫抑制疗法造成的。越来越多的关于骨髓瘤中活跃的免疫调节机制的临床前数据已开始转化为针对这些信号轴的临床试验。本综述将试图总结目前对骨髓瘤中可能重要的几种免疫检查点通路的基本生物学的理解，并提供最近和正在进行的骨髓瘤免疫检查点抑制剂临床试验的最新概述。最后，将回顾骨髓瘤免疫检查点阻断的当前挑战和未来可能的方向。
Historically, attempts at cancer immunotherapy have emphasized strategies designed to stimulate or augment the immune system into action. In the past decade, a complementary approach has developed, that of releasing immune cells from inhibitory restraint. Discoveries in the fundamental biology of how immunity is regulated, how the immune system interfaces with malignancy, and how cancer cells may exploit these processes to evade detection have all been translated into the rapidly growing field of therapeutic immune checkpoint inhibition for cancer. Myeloma is a malignancy associated with significant immune dysfunction imparted both by the disease itself as well as by many of the immunosuppressive therapies that have been used in the past. The growing body of preclinical data regarding immunoregulatory mechanisms that appear active in myeloma has begun to be translated to clinical trials targeting these signaling axes. This review will attempt to summarize the current understanding of the basic biology of several immune checkpoint pathways that may be important in myeloma and provide an up- to-date overview of recent and ongoing clinical trials of immune checkpoint inhibitors in myeloma. Finally, several current challenges and possible future directions of immune checkpoint blockade in myeloma will be reviewed.