High-risk human papillomavirus E6 inhibits monocyte differentiation to Langerhans cells

- HPV-transformed cells inhibit monocyte differentiation into Langerhans cell in culture.
- Inhibition of monocyte differentiation requires cell-to-cell contact between monocytes and HPV positive cervical cancer cells.
- Ectopic expression of HPV E6, but not E7, confers this inhibitory activity.

High-risk human papillomaviruses (HPVs) cause a variety of malignancies of the mucosal epithelium. However, the local immune evasion strategies used by HPV-transformed cells remain unclear. Here, we examined the effect of HPV-positive cancer cells on human peripheral blood monocytes, which are precursors of Langerhans cells, key antigen-presenting cells in the squamous epithelium. HPV-positive cervical cancer cells and HPV-E6 expressing cells inhibited monocyte differentiation to Langerhans cells in a contact-dependent manner. Unlike Langerhans cells, monocytes that differentiated in the presence of HPV16 E6-expressing cells exhibited high levels of endocytic activity. Our results suggest that cells infected by high-risk HPV evade immune surveillance by blocking the differentiation of monocytes into competent antigen presenting cells.