Invariant natural killer T cells are preserved in patients with glioma and exhibit antitumor lytic activity following dendritic cell-mediated expansion
Invariant natural killer T cells are preserved in patients with glioma and exhibit antitumor lytic activity following dendritic cell-mediated expansion
复制标题
DOI：
10.1002/ijc.20050
复制
发表时间：
2004-05-10
影响因子：
6.4
通讯作者：
Steinman, RM
中科院分区：
文献类型：
--
作者：
Dhodapkar, KM;Cirignano, B;Steinman, RM
脑肿瘤预后不良，迫切需要新的治疗方法。自然杀伤T细胞（NKT）是一种独特的先天淋巴细胞，具有抗肿瘤潜能。在其他形式的癌症患者中也观察到NKT细胞功能的缺陷。在这里，我们发现NKT细胞的频率和产生干扰素- γ的功能在成年胶质瘤患者（n = 9）中都得到了很好的保存，与健康对照组（n = 9）的发现相当。这些细胞可以很容易地在培养中扩增，使用装载NKT配体的自体成熟树突状细胞，a-半乳糖神经酰胺。来自胶质瘤患者的扩增的NKT细胞是功能性的，重要的是，它以配体和cd1依赖的方式杀死胶质瘤细胞。通过胶质瘤组织切片免疫组化检测CD1dd在原发性胶质瘤细胞和浸润新生血管内皮细胞上的表达。这些数据表明，靶向NKT细胞可能为神经胶质瘤的免疫治疗提供一种新的策略。(C) 2004 Wiley-Liss, Inc。
Brain tumors carry a poor prognosis, and newer approaches to their therapy are urgently needed. Natural killer T (NKT) cells are distinct innate lymphocytes with antitumor potentials. Defects in NKT cell function have been observed in patients with other forms of cancer. Here we show that both the frequency and interferon-gamma-producing function of NKT cells are well preserved in adult patients with glioma (n = 9) and comparable to findings in healthy controls (n = 9). These cells can be readily expanded in culture using autologous mature dendritic cells loaded with the NKT ligand, a-galactosyl ceramide. The expanded NKT cells from glioma patients are functional and, importantly, kill glioma cells in a ligand- and CD1d-dependent manner. Expression of CD1dd is detected both on primary glioma cells as well as endothelial Fells in infiltrating new blood vessels by immunohistochemistry of glioma tissue sections. These data suggest that targeting NKT cells may provide a novel strategy for immunotherapy of glioma. (C) 2004 Wiley-Liss, Inc.