The organotypic culture of HPV-transformed keratinocytes: an effective in vitro model for the development of new immunotherapeutic approaches for mucosal (pre)neoplastic lesions

The purpose squamous cell differentiate at manner similar carcinoma cell ability of these of this study is to develop a reliable in vitro human model to test new immunotherapeutic approaches for carcinoma that develop on mucosal surfaces. The organotypic (raft) culture permits cells to proliferate and an air-liquid interface on a dermal equivalent support. Normal keratinocytes stratify and fully differentiate in a to the normal squamous epithelial tissues while human papillomavirus-immortalized and established squamous lines exhibit dysplastic morphologies similar to (pre)neoplastic lesions seen in vivo. We have demonstrated the ability of these organotypic cultures to be manipulated by altering the epithelial stratification with cytokines (interferon-gamma and tumor necrosis factur-alpha) and by integrating activated lymphocytes or dendritic cells into the in vitro formed epithelial sheet. This model may provide a useful tool to investigate the factors contributing to the presence and function of immunocompetent cells within a neoplastic epithelium that develops on a mucosal surface. (C) 2001 Elsevier Science Ltd. All rights reserved.