Dendritic cells induce the death of human papillomavirus transformed keratinocytes

Although human papillomavirus (HPV) antigens are expressed in a majority of (pre) neoplastic lesions (squamous intraepithelial lesions; SILs) of the u terine cervix, progression to invasive cancer may occur, which suggests tha t the presentation of viral antigens to the immune system is deficient in s ome SILs. To determine whether professional antigen-presenting cells die in SILs, we assayed for the apoptosis of immature dendritic cells (DC) in org anotypic cultures of HPV-transformed keratinocytes, which reproduce many fe atures of in vivo observed SILs. Unexpectedly, the infiltration of organoty pic cultures by DC specifically induced the apoptosis of HPV+ tumor cells, whereas DC were not affected. In the same conditions and in coculture exper iments, apoptosis was not observed in normal keratinocytes. The induction o f apoptosis required membrane contacts between DC and HPV-transformed kerat inocytes. Although the HPV+ cell lines were sensitive to the effects of TRA IL, soluble TRAILR2-Fc did not block the DC-induced apoptosis. Furthermore, although FasL and Fas were detected on DC and HPV+ cell lines, respectivel y, functional analysis revealed that this pathway is not responsible for th e apoptosis induced by the DC. All together these results suggest that DC m ay be at the interface between innate and adaptive immunity by inducing the apoptosis of (pre) neoplastic cells.