Chang David H, Liu Nancy, Klimek Virginia, Hassoun Hani, Mazumder Amitabha, Nimer Stephen D, Jagannath Sundar, Dhodapkar Madhav V
Laboratory of Tumor Immunology and Immunotherapy, The Rockefeller University, New York, NY 10021, USA.
Blood. 2006 Jul 15;108(2):618-21. doi: 10.1182/blood-2005-10-4184. Epub 2006 Mar 28.
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 (Thal) analog, enhances antigen-specific expansion of NKT cells in response to the NKT ligand alpha-galactosylceramide (alpha-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.
自然杀伤T（NKT）细胞是受CD1d限制的糖脂反应性固有淋巴细胞，在抵御病原体和肿瘤方面发挥重要作用。增强NKT细胞功能的药理学方法将有助于在临床上对NKT细胞进行特异性靶向治疗。在此我们表明，来那度胺（LEN），一种新型沙利度胺（Thal）类似物，在健康供体和骨髓瘤患者中均能增强NKT细胞对NKT配体α-半乳糖神经酰胺（α-GalCer）的抗原特异性扩增。在LEN存在下激活的NKT细胞分泌干扰素-γ的能力更强。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5q缺失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介导的糖脂抗原呈递，并支持将这些药物与NKT靶向方法联合用于抗肿瘤保护。
