Adjuvant effect of a natural TLR4 ligand on dendritic cell-based cancer immunotherapy

The clinical efficacy of dendritic cell (DC) vaccine in cancer patients has been unsatisfactory due, at least in part, to the deficiency of maturation and impaired migration of ex vivo generated DCs to the draining lymph nodes. To solve this problem, we used angelan, a natural TLR4 ligand, to enhance the maturation and migration of DCs. Angelan increased the expression of MHC-I/II, CD80, and CD86, DC maturation markers, through the NF-κB pathway. This compound also increased CCR7 expression in DCs through NF-κB and p38 pathway and enhanced their migration against CCL19, which is a key chemokine that guides DCs into lymph nodes. We also showed that angelan enhanced in vivo DC homing from tissues to draining lymph nodes. When treated to DCs in vitro and vivo, angelan increased antitumor activity of DCs in B16F10 syngeneic tumor model. Taken together, the present data suggest that a natural TLR4 ligand might be helpful for overcoming the disadvantages of DC-based cancer therapy, such as impaired maturation and poor migration in cancer patients.

► TLR4 ligand induces DC maturation through NF-κB pathway.
► TLR4 ligand enhances CCR7 expression through NF-κB and p38 pathway.
► TLR4 ligand enhances DC migration to CCL19 in vitro and DC homing into the lymph nodes in vivo.
► TLR4 ligand enhances antitumor activity of DCs in animal model.