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2016 ; 17
(5
): 352-60
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Increasing the immune activity of exosomes: the effect of miRNA-depleted exosome
proteins on activating dendritic cell/cytokine-induced killer cells against
pancreatic cancer
#MMPMID27143262
Que RS
; Lin C
; Ding GP
; Wu ZR
; Cao LP
J Zhejiang Univ Sci B
2016[May]; 17
(5
): 352-60
PMID27143262
show ga
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-? (TNF-?) 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.