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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

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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