Full Text:   <1906>

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Suppl. Mater.: 

CLC number: R735.9

On-line Access: 2016-05-04

Received: 2015-12-06

Revision Accepted: 2016-02-04

Crosschecked: 2016-04-15

Cited: 4

Clicked: 3934

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Li-ping Cao

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

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Journal of Zhejiang University SCIENCE B 2016 Vol.17 No.5 P.352-360

http://doi.org/10.1631/jzus.B1500305


Increasing the immune activity of exosomes: the effect of miRNA-depleted exosome proteins on activating dendritic cell/cytokine-induced killer cells against pancreatic cancer


Author(s):  Ri-sheng Que, Cheng Lin, Guo-ping Ding, Zheng-rong Wu, Li-ping Cao

Affiliation(s):  Department of Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China; more

Corresponding email(s):   caolipingzju@126.com

Key Words:  Pancreatic cancer, Exosome, Dendritic cell, MicroRNAs


Ri-sheng Que, Cheng Lin, Guo-ping Ding, Zheng-rong Wu, Li-ping Cao. Increasing the immune activity of exosomes: the effect of miRNA-depleted exosome proteins on activating dendritic cell/cytokine-induced killer cells against pancreatic cancer[J]. Journal of Zhejiang University Science B, 2016, 17(5): 352-360.

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author="Ri-sheng Que, Cheng Lin, Guo-ping Ding, Zheng-rong Wu, Li-ping Cao",
journal="Journal of Zhejiang University Science B",
volume="17",
number="5",
pages="352-360",
year="2016",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1500305"
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%0 Journal Article
%T Increasing the immune activity of exosomes: the effect of miRNA-depleted exosome proteins on activating dendritic cell/cytokine-induced killer cells against pancreatic cancer
%A Ri-sheng Que
%A Cheng Lin
%A Guo-ping Ding
%A Zheng-rong Wu
%A Li-ping Cao
%J Journal of Zhejiang University SCIENCE B
%V 17
%N 5
%P 352-360
%@ 1673-1581
%D 2016
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1500305

TY - JOUR
T1 - Increasing the immune activity of exosomes: the effect of miRNA-depleted exosome proteins on activating dendritic cell/cytokine-induced killer cells against pancreatic cancer
A1 - Ri-sheng Que
A1 - Cheng Lin
A1 - Guo-ping Ding
A1 - Zheng-rong Wu
A1 - Li-ping Cao
J0 - Journal of Zhejiang University Science B
VL - 17
IS - 5
SP - 352
EP - 360
%@ 1673-1581
Y1 - 2016
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1500305


Abstract: 
Background: Tumor-derived exosomes were considered to be potential candidates for tumor vaccines because they are abundant in immune-regulating proteins, whereas tumor exosomal miRNAs may induce immune tolerance, thereby having an opposite immune function. Objective: This study was designed to separate exosomal protein and depleted exosomal microRNAs (miRNAs), increasing the immune activity of exosomes for activating dendritic cell/cytokine-induced killer cells (DC/CIKs) against pancreatic cancer (PC). Methods: PC-derived exosomes (PEs) were extracted from cultured PANC-1 cell supernatants and then ruptured; this was followed by ultrafiltered exosome lysates (UELs). DCs were stimulated with lipopolysaccharide (LPS), PE, and UEL, followed by co-culture with CIKs. The anti-tumor effects of DC/CIKs against PC were evaluated by proliferation and killing rates, tumor necrosis factor-α (TNF-α) and perforin secretion. Exosomal miRNAs were depleted after lysis and ultrafiltration, while 128 proteins were retained, including several immune-activating proteins. Results: UEL-stimulated DC/CIKs showed a higher killing rate than LPS- and PE-stimulated DC/CIKs. Conclusions: miRNA-depleted exosome proteins may be promising agonists for specifically activating DC/CIKs against PC.

In this manuscript the authors study the potential value of miRNA-depleted exosomes for activation of DC/CIKs. The hypothesis that "PC derived exosomal miRNAs downregulate anti-tumor activities of DC/CIKs and depletion of exosomal miRNAs may enhance the anti-tumor activity of DC/CIKs" is well-reasoned and backed by previous research findings.

DC/CIKs细胞通过无miRNA的exosome蛋白 刺激后能增强对胰腺癌细胞的免疫作用

目的:本文通过分离提取无小RNA(miRNA)的外来体(exosome)刺激树突细胞/细胞因子活化杀伤细胞(DC/CIKs),激活其对于胰腺癌细胞的免疫杀伤作用。
创新点:无miRNA的exosome超速离心裂解产物可以通过激活DC/CIKs细胞增强其对肿瘤细胞的杀伤作用。
方法:通过收集PANC-1细胞的上清并超速离心提取其中的exosome。提取的DC细胞分别通过脂多糖、肿瘤来源exosome及无miRNA的exosome刺激后,与CIK细胞共培养。通过计算增值与杀伤效率,肿瘤坏死因子-α(TNF-α)及穿孔素的分泌,比较各组间CIK细胞对胰腺癌细胞的杀伤作用。
结论:经无miRNA的exosome刺激后的CIK细胞比其他两组表现出更高的杀伤效应。实验结果表明无miRNA的exosome蛋白在DC/CIKs细胞的胰腺癌治疗中是有相当前景的激动剂。

关键词:胰腺癌;外来体;树突状细胞;小RNA

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

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[25]List of electronic supplementary materials

[26]Table S1 Proteomics identification of pancreatic cancer-derived ultrafiltered exosome lysates

[27]Fig. S1 Morphological and immunofluorescence characterization of DCs

[28]Fig. S2 Characterization of CIKs

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