CD1d expression in glioblastoma is a promising target for NKT cell-based cancer immunotherapy.
CD1d expression in glioblastoma is a promising target for NKT cell-based cancer immunotherapy.
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DOI：
10.1007/s00262-020-02742-1
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Motohashi S
中科院分区：
文献类型：
--
作者：
Hara A;Koyama-Nasu R;Takami M;Toyoda T;Aoki T;Ihara F;Kobayashi M;Hirono S;Matsutani T;Nakayama T;Iwadate Y;Motohashi S
胶质母细胞瘤是最常见和最具侵袭性的脑肿瘤，具有很高的复发率和病死率。虽然已经探索了各种治疗策略，但目前还没有有效的治疗胶质母细胞瘤的方法。最近，对恶性脑瘤的免疫治疗策略的数量已经进行了测试。不变自然杀伤T细胞(INKT)在抗肿瘤免疫中发挥重要作用。为了研究iNKT细胞是否可以靶向胶质母细胞瘤发挥抗肿瘤活性，我们研究了iNKT细胞的抗原提呈分子CD1d在胶质母细胞瘤细胞上的表达。15例患者中有10例胶质母细胞瘤细胞表达CD1d，糖脂配体冲击的CD1d阳性胶质母细胞瘤细胞在体外诱导iNKT细胞介导的细胞毒作用。虽然CD1d在胶质母细胞瘤干细胞上的表达较低，但作为最常见的分化剂，维甲酸上调了CD1d的表达，并诱导了iNKT细胞介导的细胞毒作用。此外，脑内注射人iNKT细胞可诱导NOD/SHI-SCID IL-2RγKO(NOG)小鼠原位移植瘤中CD1d阳性胶质母细胞瘤的肿瘤消退。因此，CD1d的表达为胶质母细胞瘤患者的NKT细胞免疫治疗提供了新的靶点。本文的在线版本(10.1007/s00262-020-02742-1)包含向授权用户提供的补充材料。
Glioblastoma is the most common and aggressive type of brain tumor with high recurrence and fatality rates. Although various therapeutic strategies have been explored, there is currently no effective treatment for glioblastoma. Recently, the number of immunotherapeutic strategies has been tested for malignant brain tumors. Invariant natural killer T (iNKT) cells play an important role in anti-tumor immunity. To address if iNKT cells can target glioblastoma to exert anti-tumor activity, we assessed the expression of CD1d, an antigen-presenting molecule for iNKT cells, on glioblastoma cells. Glioblastoma cells from 10 of 15 patients expressed CD1d, and CD1d-positive glioblastoma cells pulsed with glycolipid ligand induced iNKT cell-mediated cytotoxicity in vitro. Although CD1d expression was low on glioblastoma stem-like cells, retinoic acid, which is the most common differentiating agent, upregulated CD1d expression in these cells and induced iNKT cell-mediated cytotoxicity. Moreover, intracranial administration of human iNKT cells induced tumor regression of CD1d-positive glioblastoma in orthotopic xenografts in NOD/Shi-scid IL-2RγKO (NOG) mice. Thus, CD1d expression represents a novel target for NKT cell-based immunotherapy for glioblastoma patients. The online version of this article (10.1007/s00262-020-02742-1) contains supplementary material, which is available to authorized users.
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影响因子：
--
作者：
Filley AC;Henriquez M;Dey M
通讯作者：
Dey M
影响因子：
158.5
作者：
Stupp, R;Mason, WP;Ryan, G
通讯作者：
Ryan, G
影响因子：
82.9
作者：
Mount CW;Majzner RG;Sundaresh S;Arnold EP;Kadapakkam M;Haile S;Labanieh L;Hulleman E;Woo PJ;Rietberg SP;Vogel H;Monje M;Mackall CL
通讯作者：
Mackall CL
DOI：
10.1073/pnas.0509182102
发表时间：
2005-12-20
影响因子：
11.1
作者：
Sato, E;Olson, SH;Odunsi, K
通讯作者：
Odunsi, K
影响因子：
11.2
作者：
Galli, R;Binda, E;Vescovi, A
通讯作者：
Vescovi, A