Dendritic cells treated with HPV16mE7 in a three-dimensional model promote the secretion of IL-12p70 and IFN-γ

Although the human papillomavirus (HPV) DNA therapeutic vaccine represents a promising approach to the prevention and treatment of cervical cancer, the mechanism of the HPV DNA vaccine is poorly understood. Moreover, current strategies have met with only limited success in preclinical and dendritic cell-based (DC-based) clinical research. In addition, two-dimensional (2-D) DC monolayers poorly mimic the physiology function in vivo. We used a three-dimensional (3-D) DC culture model in vitro to explore the immune mechanism of the HPV DNA vaccine. DCs were generated from peripheral blood monocytes with interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The cells, growing in 3-D collagen gel, were treated with pcDNA3.1-HPV16mE7 in vitro for 48 h. Compared to DCs treated with E7 in a 2-D culture model, the expression of co-stimulatory molecules CD80 and CD40 were significantly increased in the 3-D model (p < 0.05), and a remarkable increase of IL-12 p70 was observed. However, we did not detect any obvious change in IL-10 in 3-D culture. In addition, we found that IFN-γ expression increased when HPV16mE7-DC cells were co-cultured with T-cells for 96 h in the 3-D model, and HPV16mE7-DCs stimulated the proliferation of T lymphocytes more efficiently in the 3-D model than in the 2-D model (p < 0.05). These results suggest that DCs in 3-D culture model have a notable effect on the enhancement of the HPV16 DNA vaccine's immune reaction and indicate that the DC-based 3-D model is a novel approach to study the HPV vaccine.

Research Highlights
► DCs treated with HPV16mE7 in 3-D model promote the secretion of IL-12p70 and IFN-γ.
► Transfected DCs in 3-D culture does not increase IL-10 secretion.
► DCs in 3-D culture enhance HPV16 DNA vaccine’s immune reaction.
► DC-based 3-D model is a novel approach to study the HPV vaccine.