VISTA信号阻断对DC-CIK杀伤恶性肿瘤细胞的影响

doi:10.3969/j.issn.1673-8640.2018.10.015

检验医学 ›› 2018, Vol. 33 ›› Issue (10): 933-937.DOI: 10.3969/j.issn.1673-8640.2018.10.015

VISTA信号阻断对DC-CIK杀伤恶性肿瘤细胞的影响

杨惠宽¹, 苑召虎¹, 陈小洁¹, 魏亚明¹, 谌丹丹²

1.广州医科大学附属市一人民医院输血科,广东广州 510180
2.广州医科大学附属市一人民医院放射科,广东广州 510180

收稿日期:2017-09-16 出版日期:2018-10-30 发布日期:2018-10-23
作者简介:null
作者简介：杨惠宽,女,1973年生,学士,主管技师,主要从事细胞免疫研究工作。
基金资助:
国家自然科学基金项目（81702058）;广州市卫生计生科技一般引导项目（20161A011010）

Inhibition of DC-CIK VISTA signal for improving the anti-tumor effect of malignant tumor cells

YANG Huikuan¹, YUAN Zhaohu¹, CHEN Xiaojie¹, WEI Yaming¹, CHEN Dandan²

1. Department of Blood Transfusion,the First Affiliated Hospital of Guangzhou Medical University,Guangzhou 510180,Guangdong,China
2. Department of Radiology,the First Affiliated Hospital of Guangzhou Medical University,Guangzhou 510180,Guangdong,China

Received:2017-09-16 Online:2018-10-30 Published:2018-10-23

摘要/Abstract

摘要：

目的探讨阻断树突状细胞联合细胞因子诱导的杀伤细胞（DC-CIK）表面T细胞激活抑制物免疫球蛋白可变区结构域（VISTA）抗原,抑制由VISTA信号活化引起的免疫负调节,对其杀伤恶性肿瘤细胞的活性的影响。方法采用流式细胞术分析DC-CIK与抗VISTA抗体的结合情况,用3-（4,5-二甲基噻唑-2）-2,5-二苯基四氮唑溴盐（MTT）法检测DC-CIK对人慢性髓系白血病细胞株K562的杀伤效应。通过细胞计数及流式细胞术分析VISTA抗体对DC-CIK增殖和分化的影响。结果培养成熟的DC-CIK与抗VISTA抗体温育后,其抗体结合率可达（10.26±0.57）%。随着效应细胞（DC-CIK）与靶细胞（K562细胞）比例的增高,实验组（经抗VISTA抗体处理的DC-CIK）和对照组（未经处理的DC-CIK）的杀伤活性均显著增高;当效应细胞∶靶细胞为10∶1和20∶1时,实验组的杀伤活性分别为（77.3±6.8）%和（92.8±5.9）%,均明显高于对照组 [（64.8±4.0）%、（81.8±5.4）%]（P<0.01）。温育54 h后,实验组的细胞数明显高于对照组（P<0.01）,为对照组的1.35倍。实验组CD3⁺CD56⁺自然杀伤性T细胞（NKT）比例为（35.12±2.13）%,明显高于对照组[（21.35±1.32）%]（P<0.01）。结论阻断DC-CIK VISTA信号可促进DC-CIK的增殖和分化,增强其对肿瘤细胞的杀伤效应。

关键词: 树突状细胞联合细胞因子诱导的杀伤细胞, T细胞激活抑制物免疫球蛋白可变区结构域, 增殖, 分化, 免疫逃逸

Abstract:

Objective To inhibit the antigen of anti-V-domain Ig suppressor of T cell activation（VISTA） antibody on dendritic cell-cytokine-induced killer cell（DC-CIK） and the down regulation due to VISTA signal activation,and to evaluate the anti-tumor effect of malignant tumor cells. Methods Anti-VISTA antibody on DC-CIK was determined by flow cytometry. The killing activity of DC-CIK on human chronic myeloid leukemia cell line K562 was analyzed by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide（MTT）. The effect of anti-VISTA antibody on the proliferation and differentiation of DC-CIK was analyzed by cell count analysis and flow cytometry,respectively. Results After the incubation of mature DC-CIK with anti-VISTA antibody,the percentage of anti-VISTA antibody positive cells was（10.26±0.57）%. With the increasing of effector cells（DC-CIK）-to-target cells（K562） ratio,the killing activities in experimental group（DC-CIK cell treated with anti-VISTA antibody） and control group（untreated DC-CIK cell） were increased. When effector cells-to-target cells ratios of 10∶1 and 20∶1,the killing activities in experimental group were（77.3±6.8）% and（92.8±5.9）%,respectively,which were higher than those in control group [（64.8±4.0）% and（81.8±5.4）%]（P<0.01）. After incubation for 54 h,the cell number of experimental group was 1.35-time higher than that of control group（P<0.01）. The percentage of CD3⁺CD56⁺ natural killer T cells（NKT） in experimental group [（35.12±2.13）%] was higher than that in control group [（21.35±1.32）%]（P<0.01）. Conclusions The inhibition of DC-CIK VISTA signal can improve the anti-tumor effect of malignant tumor cells through the proliferation and differentiation of DC-CIK.

Key words: Dendritic cell-cytokine-induced killer cell, V-domain Ig suppressor of T cell activation, Proliferation, Differentiation, Immune escape

中图分类号:

R446.61

杨惠宽, 苑召虎, 陈小洁, 魏亚明, 谌丹丹. VISTA信号阻断对DC-CIK杀伤恶性肿瘤细胞的影响[J]. 检验医学, 2018, 33(10): 933-937.

YANG Huikuan, YUAN Zhaohu, CHEN Xiaojie, WEI Yaming, CHEN Dandan. Inhibition of DC-CIK VISTA signal for improving the anti-tumor effect of malignant tumor cells[J]. Laboratory Medicine, 2018, 33(10): 933-937.

图/表 3

参考文献 10

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VISTA信号阻断对DC-CIK杀伤恶性肿瘤细胞的影响

Inhibition of DC-CIK VISTA signal for improving the anti-tumor effect of malignant tumor cells

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