Full Text:   <2755>

Summary:  <2103>

Suppl. Mater.: 

CLC number: R735.9

On-line Access: 2024-08-27

Received: 2023-10-17

Revision Accepted: 2024-05-08

Crosschecked: 2016-04-15

Cited: 4

Clicked: 5271

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Li-ping Cao

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

-   Go to

Article info.
Open peer comments

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.

@article{title="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="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"
}

%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

Reference

[1]Azmi, A.S., Bao, B., Sarkar, F.H., 2013. Exosomes in cancer development, metastasis, and drug resistance: a comprehensive review. Cancer Metastasis Rev., 32(3-4):623-642.

[2]Baj-Krzyworzeka, M., Szatanek, R., Weglarczyk, K., et al., 2007. Tumour-derived microvesicles modulate biological activity of human monocytes. Immunol. Lett., 113(2):76-82.

[3]Chen, J., Ding, G., Chen, W., 2013. The anti-tumor activity of DC/CTL induced by cholangiocarcinoma derived exosome and its ultrafiltered lysate. Chin. J. Exp. Surg., 30:2258-2261.

[4]Chung, M.J., Park, J.Y., Bang, S., et al., 2014. Phase II clinical trial of ex vivo-expanded cytokine-induced killer cells therapy in advanced pancreatic cancer. Cancer Immunol. Immunother., 63(9):939-946.

[5]Duke-Cohan, J.S., Tang, W., Schlossman, S.F., 2002. Attractin: a cub-family protease involved in T cell-monocyte/macrophage interactions. In: Langner, J., Ansorge, S. (Eds.), Cellular Peptidases in Immune Functions and Diseases 2. Springer US, p.173-185.

[6]Hartwig, W., Werner, J., Jäger, D., et al., 2013. Improvement of surgical results for pancreatic cancer. Lancet Oncol., 14(11):e476-e485.

[7]Hong, C.S., Muller, L., Boyiadzis, M., et al., 2014. Isolation and characterization of CD34+ blast-derived exosomes in acute myeloid leukemia. PLoS ONE, 9(8):e103310.

[8]Hunyadi, J., András, C., Szabó, I., et al., 2014. Autologous dendritic cell based adoptive immunotherapy of patients with colorectal cancer-a phase I-II study. Pathol. Oncol. Res., 20(2):357-365.

[9]Kalra, H., Adda, C.G., Liem, M., et al., 2013. Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma. Proteomics, 13(22):3354-3364.

[10]Koga, K., Matsumoto, K., Akiyoshi, T., et al., 2005. Purification, characterization and biological significance of tumor-derived exosomes. Anticancer Res., 25:3703-3707.

[11]Li, G.H., Arora, P.D., Chen, Y., et al., 2012. Multifunctional roles of gelsolin in health and diseases. Med. Res. Rev., 32(5):999-1025.

[12]Ma, C., Nong, K., Wu, B., et al., 2014. miR-212 promotes pancreatic cancer cell growth and invasion by targeting the hedgehog signaling pathway receptor patched-1. J. Exp. Clin. Cancer Res., 33:54.

[13]Melo, S.A., Sugimoto, H., O'Connell, J.T., et al., 2014. Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer Cell, 26(5):707-721.

[14]Muller, L., Hong, C.S., Stolz, D.B., et al., 2014. Isolation of biologically-active exosomes from human plasma. J. Immunol. Methods, 411:55-65.

[15]Neumann, A.K., Thompson, N.L., Jacobson, K., 2008. Distribution and lateral mobility of DC-SIGN on immature dendritic cells-implications for pathogen uptake. J. Cell Sci., 121(5):634-643.

[16]Park, J.K., Henry, J.C., Jiang, J., et al., 2011. miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor. Biochem. Biophys. Res. Commun., 406(4):518-523.

[17]Pitt, J.M., Charrier, M., Viaud, S., et al., 2014. Dendritic cell-derived exosomes as immunotherapies in the fight against cancer. J. Immunol., 193(3):1006-1011.

[18]Tan, A., De La Peña, H., Seifalian, A.M., 2010. The application of exosomes as a nanoscale cancer vaccine. Int. J. Nanomed., 5(1):889-900.

[19]Thota, R., Pauff, J.M., Berlin, J.D., 2014. Treatment of metastatic pancreatic adenocarcinoma: a review. Oncology, 28:70-74.

[20]Vincent, A., Herman, J., Schulick, R., et al., 2011. Pancreatic cancer. Lancet, 378(9791):607-620.

[21]Wang, X., Yu, W., Li, H., et al., 2014. Can the dual-functional capability of CIK cells be used to improve antitumor effects Cell. Immunol., 287(1):18-22.

[22]Wolfers, J., Lozier, A., Raposo, G., et al., 2001. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat. Med., 7(3):297-303.

[23]Zhou, M., Chen, J., Zhou, L., et al., 2014. Pancreatic cancer derived exosomes regulate the expression of TLR4 in dendritic cells via miR-203. Cell. Immunol., 292(1-2):65-69.

[24]Zhou, W., Fong, M.Y., Min, Y., et al., 2014. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis. Cancer Cell, 25(4):501-515.

[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

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE