Full Text:   <1676>

Summary:  <1367>

CLC number: R73-37

On-line Access: 2016-07-06

Received: 2015-11-04

Revision Accepted: 2016-01-22

Crosschecked: 2016-06-18

Cited: 2

Clicked: 3108

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Li-ping Cao

http://orcid.org/0000-0003-0399-1228

Jiong-huang Chen

http://orcid.org/0000-0002-8932-9261

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Journal of Zhejiang University SCIENCE B 2016 Vol.17 No.7 P.537-544

http://doi.org/10.1631/jzus.B1500266


Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin


Author(s):  Jiong-huang Chen, Jian-yang Xiang, Guo-ping Ding, Li-ping Cao

Affiliation(s):  Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China

Corresponding email(s):   caolipingzju@126.com

Key Words:  Cholangiocarcinoma, Tumor-derived exosomes, Cytokine-induced killer cells, Immune escape


Jiong-huang Chen, Jian-yang Xiang, Guo-ping Ding, Li-ping Cao. Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin[J]. Journal of Zhejiang University Science B, 2016, 17(7): 537-544.

@article{title="Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin",
author="Jiong-huang Chen, Jian-yang Xiang, Guo-ping Ding, Li-ping Cao",
journal="Journal of Zhejiang University Science B",
volume="17",
number="7",
pages="537-544",
year="2016",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1500266"
}

%0 Journal Article
%T Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin
%A Jiong-huang Chen
%A Jian-yang Xiang
%A Guo-ping Ding
%A Li-ping Cao
%J Journal of Zhejiang University SCIENCE B
%V 17
%N 7
%P 537-544
%@ 1673-1581
%D 2016
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1500266

TY - JOUR
T1 - Cholangiocarcinoma-derived exosomes inhibit the antitumor activity of cytokine-induced killer cells by down-regulating the secretion of tumor necrosis factor-α and perforin
A1 - Jiong-huang Chen
A1 - Jian-yang Xiang
A1 - Guo-ping Ding
A1 - Li-ping Cao
J0 - Journal of Zhejiang University Science B
VL - 17
IS - 7
SP - 537
EP - 544
%@ 1673-1581
Y1 - 2016
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1500266


Abstract: 
Objective: The aim of our study is to observe the impact of cholangiocarcinoma-derived exosomes on the antitumor activities of cytokine-induced killer (CIK) cells and then demonstrate the appropriate mechanism. Methods: tumor-derived exosomes (TEXs), which are derived from RBE cells (human cholangiocarcinoma line), were collected by ultracentrifugation. CIK cells induced from peripheral blood were stimulated by TEXs. Fluorescence-activated cell sorting (FACS) was performed to determine the phenotypes of TEX-CIK and N-CIK (normal CIK) cells. The concentrations of tumor necrosis factor-α (TNF-α) and perforin in the culture medium supernatant were examined by using an enzyme-linked immunosorbent assay (ELISA) kit. A CCK-8 kit was used to evaluate the cytotoxic activity of the CIK cells to the RBE cell line. Results: The concentrations of TNF-α and perforin of the group TEX-CIK were 138.61 pg/ml and 2.41 ng/ml, respectively, lower than those of the group N-CIK 194.08 pg/ml (P<0.01) and 3.39 ng/ml (P<0.05). The killing rate of the group TEX-CIK was 33.35%, lower than that of the group N-CIK (47.35% (P<0.01)). The population of CD3+, CD8+, NK (CD56+), and CD3+CD56+ cells decreased in the TEX-CIK group ((63.2±6.8)%, (2.5±1.0)%, (0.53±0.49)%, (0.45±0.42)%) compared with the N-CIK group ((90.3±7.3)%, (65.7±3.3)%, (4.2±1.2)%, (15.2±2.7)%), P<0.01. Conclusions: Our results suggest that RBE cells-derived exosomes inhibit the antitumor activity of CIK cells by down-regulating the population of CD3+, CD8+, NK (CD56+), and CD3+CD56+ cells and the secretion of TNF-α and perforin. TEX may play an important role in cholangiocarcinoma immune escape.

胆管癌外泌体通过抑制肿瘤坏死因子α与穿孔素分泌使细胞因子诱导的杀伤细胞抗肿瘤活性下降

目的:探索胆管癌来源外泌体(TEX)对细胞因子诱导的杀伤细胞(CIK)抗肿瘤活性的影响,并初步探讨其作用机制。
创新点:首次通过体外实验证明TEX可引起CIK抗肿瘤活性下降,且此作用与肿瘤坏死因子α(TNF-α)和穿孔素表达抑制相关。
方法:采用超速离心法提取人胆管癌细胞(RBE)来源的外泌体,同时CIK通过人外周血培养获得。将TEX负载到CIK培养体系中作为TEX-CIK组,不加TEX的CIK作为N-CIK组。流式细胞仪检测两组CIK细胞表型变化,酶联免疫吸附法(ELISA)检测两组培养基上清液中TNF-α和穿孔素的浓度,CCK-8法检测CIK对RBE细胞的杀伤活性。
结论:TEX能降低CIK细胞CD3+、CD8+、NK(CD56+)以及CD3+CD56+比例,并且抑制TNF-α和穿孔素表达,从而降低CIK细胞的抗肿瘤效应。

关键词:胆管癌;肿瘤来源外泌体;细胞因子诱导的杀伤细胞;免疫逃逸

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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