Medulloblastoma expresses CD1d and can be targeted for immunotherapy with NKT cells

被引：59

作者：

Liu, Daofeng ^{[1
,3
]}

Song, Liping ^{[1
,3
]}

Brawley, Vita S. ^{[1
,3
]}

Robison, Nathan ^{[4
,5
]}

Wei, Jie ^{[1
,3
]}

Gao, Xiuhua ^{[1
,3
]}

Tian, Gengwen ^{[1
,3
]}

Margol, Ashley ^{[4
,5
]}

Ahmed, Nabil ^{[1
,3
]}

Asgharzadeh, Shahab ^{[4
,5
]}

Metelitsa, Leonid S. ^{[1
,2
,3
]}

机构：

[1] Baylor Coll Med, Dept Pediat, Texas Childrens Canc Ctr, Houston, TX 77030 USA

[2] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA

[3] Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA

[4] Univ So Calif, Div Hematol Oncol, Dept Pediat, Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA

[5] Univ So Calif, Keck Sch Med, Los Angeles, CA 90027 USA

来源：

CLINICAL IMMUNOLOGY | 2013年 / 149卷 / 01期

基金：

美国国家卫生研究院;

关键词：

Medulloblastoma; NKT cells; CD1d; Cellular immunotherapy; Brain tumors; KILLER T-CELLS; SUBSETS; SUBGROUPS; THERAPY; LIGAND; LINE;

D O I：

10.1016/j.clim.2013.06.005

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：55 / 64

页数：10

共 37 条

[1] Regression of experimental medulloblastoma following transfer of HER2-specific T cells [J].