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醋酸格拉替雷、富马酸二甲酯和富马酸单甲酯上调自然杀伤细胞表面CCR10的表达并增强其趋化性和细胞毒性。

Glatiramer Acetate, Dimethyl Fumarate, and Monomethyl Fumarate Upregulate the Expression of CCR10 on the Surface of Natural Killer Cells and Enhance Their Chemotaxis and Cytotoxicity.

作者信息

Maghazachi Azzam A, Sand Kristin L, Al-Jaderi Zaidoon

机构信息

Department of Clinical Sciences, College of Medicine, and the Sharjah Institute for Medical Research (SIMR), University of Sharjah , Sharjah , United Arab Emirates.

University of Oslo , Oslo , Norway.

出版信息

Front Immunol. 2016 Oct 19;7:437. doi: 10.3389/fimmu.2016.00437. eCollection 2016.

Abstract

harnessing of immune cells is the most important advance in the field of cancer immunotherapy. Results shown in the current paper may be used to harness natural killer (NK) cells . It is observed that drugs used to treat multiple sclerosis such as glatiramer acetate, dimethyl fumarate, and monomethyl fumarate upregulate the expression of chemokines receptor 10 (CCR10) on the surface of human IL-2-activated NK cells. This is corroborated with increased chemotaxis of these cells toward the concentration gradients of the ligands for CCR10, namely CCL27 and CCL28. It is also demonstrated that these three drugs enhance NK cell cytotoxicity against tumor target cells, an activity that is abrogated by prior incubation of the cells with anti-CCR10 antibody. Because CCL27 and CCL28 are secreted by selective tumor types such as malignant melanoma, squamous cell carcinomas, and colorectal cancer, respectively, it is hypothesized that activated NK cells may be harnessed with any of these drugs before utilizing them as a therapeutic modality for cancer.

摘要

免疫细胞的利用是癌症免疫治疗领域最重要的进展。本文所示结果可用于利用自然杀伤(NK)细胞。据观察,用于治疗多发性硬化症的药物,如醋酸格拉替雷、富马酸二甲酯和富马酸单甲酯,可上调人白细胞介素-2激活的NK细胞表面趋化因子受体10(CCR10)的表达。这些细胞对CCR10配体(即CCL27和CCL28)的浓度梯度趋化性增强,证实了这一点。还证明这三种药物增强了NK细胞对肿瘤靶细胞的细胞毒性,用抗CCR10抗体预先孵育细胞可消除这种活性。由于CCL27和CCL28分别由选择性肿瘤类型(如恶性黑色素瘤、鳞状细胞癌和结直肠癌)分泌,因此推测在将活化的NK细胞用作癌症治疗手段之前,可使用上述任何一种药物来利用它们。

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