کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6087638 | 1207375 | 2013 | 10 صفحه PDF | دانلود رایگان |

- Tumor cells in a subset of patients with medulloblastoma express CD1d.
- CD1d is expression is higher in Shh molecular subgroup compared with Group 4.
- CD1d-positive medulloblastoma cells cross-present glycolipids to NKT cells.
- Treatment with NKT cells results in regression of intracranial tumors in mice.
- NKT cells are preserved in peripheral blood of children with medulloblastoma.
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.
Journal: Clinical Immunology - Volume 149, Issue 1, October 2013, Pages 55-64