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

增强外泌体的免疫活性:miRNA 缺失的外泌体蛋白对激活树突状细胞/细胞因子诱导的杀伤细胞对抗胰腺癌的影响

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作者:Ri-Sheng Que, Cheng Lin, Guo-Ping Ding, Zheng-Rong Wu, Li-Ping Cao

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.

Conclusions

miRNA-depleted exosome proteins may be promising agonists for specifically activating DC/CIKs against 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.

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).

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.

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