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. 2016 May;17(5):352-60.
doi: 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

Ri-Sheng Que  1 , Cheng Lin  2 , Guo-Ping Ding  2 , Zheng-Rong Wu  2 , Li-Ping Cao  2
Affiliations

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

Ri-Sheng Que et al. J Zhejiang Univ Sci B. 2016 May.

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.

Keywords: Dendritic cell; Exosome; MicroRNAs; Pancreatic cancer.

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Conflict of interest statement

Compliance with ethics guidelines: Ri-sheng QUE, Cheng LIN, Guo-ping DING, Zheng-rong WU, and Li-ping CAO declare that they have no conflict of interest.

This article does not contain any studies with human or animal subjects performed by any of the authors.

Figures

Fig. 1
Fig. 1
PANC-1-derived exosome (a) and ultrafiltered exosome lysate (b) viewed under electron microscopy
Fig. 2
Fig. 2
Exosomal and UEL RNA electrophoresis PANC-1 exosomes contained integral 28S RNA, 18S RNA, and miRNAs, while miRNAs in UEL were depleted and mRNA was degraded after ultrafiltration. M: RNA markers; E: exosomal RNA; U: UEL RNA
Fig. 3
Fig. 3
Western blot of TNF-α(a) and perforin (b) in LPS-DCs-CIKs, PE-DCs-CIKs and UEL-DCs-CIKs L: LPS-DCs-CIKs; P: PE-DCs-CIKs; U: UEL-DCs-CIKs. TNF-α and perforin were observed in the three CIK groups. Strong expressions of both proteins were observed in LPS- and UEL-DCs-CIKs, while moderate expression was detected in PE-DCs-CIKs
See this image and copyright information in PMC

Comment in

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