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Development of chemokine-cocktail therapy against hyman malignant gliomas using lymphocyte-specific chemokines

使用淋巴细胞特异性趋化因子开发针对海曼恶性胶质瘤的趋化因子混合物疗法

基本信息

批准号：
13671451
负责人：
TAKESHIMA Hideo
金额：
$ 2.18万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671451/
关键词：
Chemokine Glioma LARC TARC Immunotherapy LARK

项目摘要

Lymphocytes are frequently observed in human malignant glioma, the mechanism(s) underlying their appearance is not fully understood. To clarify tumor immunity in malignant gliomas, we analyzed the expression of 8 novel lymphocyte-specific chemokines in human glioma cell lines and glioma tissues by RT-PCR, Northern blot, immunoblot and immunohistochemistry, and examined the correlation with the infiltration of various subsets of lymphocytes. For the 8 chemokines examined (LARC, TARC, ELC, SLC, PARC, LEC, HCC-2, and SCM-1a), expression of LARC was clearly detectable in all 12 glioma cell lines by RT-PCR. Additionally, expression of TARC and SCM-1a was detectable in the majority of glioma cell lines. However, the expression level of most chemokines was low, so that Northern blot analysis could not demonstrate their expression with the exception of LARC in 2 cell lines. Expression of LARC mRNA and LARC protein was strongly induced by phorbol myristate ester in U87 MG cells. The production of LARC protein was demonstrated in 4 of 8 glioblastoma tissues by immunoblot, and 9 of 33 samples (27.3%) by immunohistochemistry. Interestingly, the positivist of LARC staining was significantly correlated with the infiltration of CD8-, CD4-, and CD45R0-positive cells (p<0.001).Although the constitutive expression level of LARC is low, certain stimulations could strongly induce its expression, and play a crucial role in the tumor immunity of human malignant glioma.

淋巴细胞是恶性胶质瘤中常见的细胞，其发生机制尚不完全清楚。为了阐明恶性胶质瘤的肿瘤免疫机制，我们采用RT-PCR、北方印迹、免疫印迹和免疫组化方法分析了8种新型淋巴细胞特异性趋化因子在人脑胶质瘤细胞系和胶质瘤组织中的表达，并检测了其与不同淋巴细胞亚群浸润的相关性。对于所检查的8种趋化因子（LARC、TARC、ELC、SLC、PARC、LEC、HCC-2和SCM-1a），通过RT-PCR在所有12种胶质瘤细胞系中清楚地检测到LARC的表达。此外，在大多数胶质瘤细胞系中可检测到TARC和SCM-1a的表达。然而，大多数趋化因子的表达水平较低，因此北方印迹分析不能证明它们的表达，但LARC在2个细胞系中除外。在U87 MG细胞中，佛波醇肉豆蔻酸酯强烈诱导LARC mRNA和LARC蛋白的表达。免疫印迹法检测8例胶质母细胞瘤组织中有4例表达LARC蛋白，免疫组化法检测33例胶质母细胞瘤组织中有9例（27.3%）表达LARC蛋白。有趣的是，LARC染色阳性与CD 8-、CD 4-和CD 45 R 0阳性细胞的浸润呈显著相关（p<0.001），尽管LARC的组成性表达水平较低，但某些刺激可以强烈诱导其表达，并在人类恶性胶质瘤的肿瘤免疫中发挥关键作用。