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.
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.
authors.affiliation: Department of Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
authors.forename: Ri-Sheng
authors.initials: RS
authors.lastname: Que
authors.affiliation: Department of Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, China.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Ding
authors.affiliation: Department of Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, China.
authors.forename: Zheng-Rong
authors.initials: ZR
authors.lastname: Wu
authors.affiliation: Department of Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310020, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Cao
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002853:Chromatography, Liquid; D055612:Cytokine-Induced Killer Cells / Q000166:cytology / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007107:Immune System; D008070:Lipopolysaccharides; D035683:MicroRNAs / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism*; D040901:Proteomics; D021241:Spectrometry, Mass, Electrospray Ionization; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D035683:MicroRNAs; D014409:Tumor Necrosis Factor-alpha
keywords: Dendritic cell; Exosome; MicroRNAs; Pancreatic cancer