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 ab ility of these of this study is to develop a reliable in vitro human model to test new immunotherapeutic approaches for carcinoma that develop on muco sal surfaces. The organotypic (raft) culture permits cells to proliferate a nd an air-liquid interface on a dermal equivalent support. Normal keratinoc ytes stratify and fully differentiate in a to the normal squamous epithelia l tissues while human papillomavirus-immortalized and established squamous lines exhibit dysplastic morphologies similar to (pre)neoplastic lesions se en 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 activ ated lymphocytes or dendritic cells into the in vitro formed epithelial she et. This model may provide a useful tool to investigate the factors contrib uting to the presence and function of immunocompetent cells within a neopla stic epithelium that develops on a mucosal surface. (C) 2001 Elsevier Scien ce Ltd. All rights reserved.