HPV18-E6 promotes tumor cell migration by down regulating Toll-like receptors in cancer microenvironment

Background: To explore the underlying mechanism of the regulatory effect of HPV-associated cancer cells on immune cells of the cervical cancer microenvironment. Methods: : Immature dendritic cells (imDCs) were obtained from primary mouse bone marrow cells, which were induced in 500 ng/mL LPS for 18 h to get mature dendritic cells (mDCs). DCs were then identified by measuring CD11c, CD80 and CD86 by flow cytometry. Protein levels of TLR3, TLR4 and TLR7 in imDCs and mDCs were examined by Western blot. H8 cells transfected with shHPV18-E6 or Hela cells transfected with HPV18-E6 siRNA were co-cultured with mDCs for 24 h, followed by protein levels of TLR3, TLR4 and TLR7, cell apoptosis and migration. Results: : Protein levels of TLR3, TLR4 and TLR7 were significantly higher in mDCs than in imDCs. A higher migratory rate and higher protein levels of TLR3, TLR4 and TLR7 were detected in H8 cells transfected with shHPV18-E6 co-cultured with mDCs than those of controls; While the opposite results were detected in Hela cells transfected with HPV18-E6 siRNA that were co-cultured with mDCs. Conclusion: TLR3, TLR4 and TLR7 are upregulated in mDCs. HPV18-E6 mediates immune cells in the cervical cancer microenvironment via regulating Toll-like receptors (TLRs), thereby achieving immune escape and promoting the migration of cervical cancer cells.