Texas Children's Cancer Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA.
Clin Immunol. 2013 Oct;149(1):55-64. doi: 10.1016/j.clim.2013.06.005. Epub 2013 Jun 18.
Medulloblastoma (MB) is the most common malignant brain tumor of childhood. Current therapies are toxic and not always curative that necessitates development of targeted immunotherapy. However, little is known about immunobiology of this tumor. In this study, we show that MB cells in 9 of 20 primary tumors express CD1d, an antigen-presenting molecule for Natural Killer T cells (NKTs). Quantitative RT-PCR analysis of 61 primary tumors revealed an elevated level of CD1d mRNA expression in a molecular subgroup characterized by an overactivation of Sonic Hedgehog (SHH) oncogene compared with Group 4. CD1d-positive MB cells cross-presented glycolipid antigens to activate NKT-cell cytotoxicity. Intracranial injection of NKTs resulted in regression of orthotopic MB xenografts in NOD/SCID mice. Importantly, the numbers and function of peripheral blood type-I NKTs were preserved in MB patients. Therefore, CD1d is expressed on tumor cells in a subset of MB patients and represents a novel target for immunotherapy.
髓母细胞瘤（MB）是儿童最常见的恶性脑肿瘤。目前的治疗方法具有毒性，并不总是能治愈，因此需要开发靶向免疫疗法。然而，人们对这种肿瘤的免疫生物学知之甚少。在这项研究中，我们发现 20 个原发性肿瘤中的 9 个肿瘤细胞表达 CD1d，这是一种天然杀伤 T 细胞（NKT）的抗原呈递分子。对 61 个原发性肿瘤的定量 RT-PCR 分析显示，与第 4 组相比，分子亚组中 Sonic Hedgehog (SHH) 癌基因过度激活，CD1d mRNA 表达水平升高。CD1d 阳性 MB 细胞交叉呈递糖脂抗原，激活 NKT 细胞的细胞毒性。NKT 细胞颅内注射可使 NOD/SCID 小鼠原位 MB 异种移植物消退。重要的是，MB 患者的外周血 I 型 NKT 细胞数量和功能保持不变。因此，CD1d 在一部分 MB 患者的肿瘤细胞上表达，代表了一种新的免疫治疗靶点。
