Pancreatic cancer derived exosomes regulate the expression of TLR4 in dendritic cells via miR-203

• We purified the exosomes from medium of pancreatic cancer through centrifugation.
• Exosome protein markers CD63, HSP70, and TSG101 in exosomes consist with panc-1 cells.
• We verified the expression of miR-203 in exosomes and pancreatic cancer cells.
• The expression of miR-203 was in accordance with exosomes and panc-1 cells.
• We found exosomes via miR-203 regulate TLR4 of dendritic cells and influence TNF-α and IL-12.

MicroRNAs (miRNAs) are aberrant in many human tumors which can be transferred to immune cells by tumor-derived exosomes. Dendritic cells (DCs) play an important role in activation of immune response. However, the effect of tumor-derived exosomes on toll-like receptor (TLR) in DCs remains unclear. We investigated the influence of pancreatic cancer derived exosomes on TLR4, and downstream cytokines via miR-203. Our results showed that miR-203 expressed in panc-1 cells and exosomes, and upregulated in exosomes-treated DCs. TLR4 decreased after treatment of exosomes and miR-203 mimics, while increased in exosomes-treated DCs by miR-203 inhibitors. But the mRNA level of TLR4 was not significantly different between DCs and exosomes-treated DCs. Tumor necrosis factor-α (TNF-α) and interleukin-12 (IL-12) also decreased under treatment of exosomes and miR-203 mimics, both of which increased in exosomes-treated DCs by miR-203 inhibitors. Collectively, pancreatic cancer derived exosomes downregulate TLR4 and downstream cytokines in DCs via miR-203.