Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications
Enhancement of ligand-dependent activation of human natural killer T cells by lenalidomide: therapeutic implications
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DOI：
10.1182/blood-2005-10-4184
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发表时间：
2006-07-15
期刊：
影响因子：
20.3
通讯作者：
Dhodapkar, Madhav V.
中科院分区：
文献类型：
--
作者：
Chang, David H.;Liu, Nancy;Dhodapkar, Madhav V.
自然杀伤 T (NKT) 细胞是 CD1d 限制性糖脂反应性先天淋巴细胞，在抵御病原体和肿瘤方面发挥着重要作用。增强 NKT 细胞功能的药理学方法将有助于临床上特定的 NKT 靶向治疗。在这里，我们发现来那度胺 (LEN) 是一种新型沙利度胺 (Thai) 类似物，在健康供体和骨髓瘤患者中，可增强 NKT 细胞对 NKT 配体 e-半乳糖神经酰胺 (a-GalCer) 的抗原特异性扩增。 LEN 存在时激活的 NKT 细胞具有更强的分泌干扰素-γ 的能力。地塞米松 (DEX) 加 LEN 存在时，NKT 细胞的抗原依赖性激活比单独使用 DEX 时更强。 LEN/Thal 治疗还导致骨髓瘤和 del5q 骨髓增生异常综合征患者体内 NKT 细胞增加。这些数据共同表明，LEN 及其类似物增强了 CD1d 介导的糖脂抗原的呈递，并支持将这些药物与 NKT 靶向方法相结合以预防肿瘤。
Natural killer T (NKT) cells are CD1d-restricted glycolipid reactive innate lymphocytes that play an important role in protection from pathogens and tumors. Pharmacologic approaches to enhance NKT cell function will facilitate specific NKT targeting in the clinic. Here we show that lenalidomide (LEN), a novel thalidomide (Thai) analog, enhances antigen-specific expansion of NKT cells in response to the NKT ligand et-galactosylceramide (a-GalCer) in both healthy donors and patients with myeloma. NKT cells activated in the presence of LEN have greater ability to secrete interferon-gamma. Antigen-dependent activation of NKT cells was greater in the presence of dexamethasone (DEX) plus LEN than with DEX alone. Therapy with LEN/Thal also led to an increase in NKT cells in vivo in patients with myeloma and del5q myelodysplastic syndrome. Together these data demonstrate that LEN and its analogues enhance CD1d-mediated presentation of glycolipid antigens and support combining these agents with NKT targeted approaches for protection against tumors.