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

P Delvenne; P Hubert; N Jacobs; S L Giannini; L Havard; I Renard; D Saboulard; J Boniver

doi:10.1016/s0264-410x(00)00489-8

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

Vaccine. 2001 Mar 21;19(17-19):2557-64. doi: 10.1016/s0264-410x(00)00489-8.

Authors

P Delvenne¹, P Hubert, N Jacobs, S L Giannini, L Havard, I Renard, D Saboulard, J Boniver

Affiliation

¹ Department of Pathology B35, University Hospital of Liège, CHU Sart Tilman, 4000, Liège, Belgium. p.delvenne@ulg.ac.be

PMID: 11257392
DOI: 10.1016/s0264-410x(00)00489-8

Abstract

The purpose of this study is to develop a reliable in vitro human model to test new immunotherapeutic approaches for squamous cell carcinoma that develop on mucosal surfaces. The organotypic (raft) culture permits cells to proliferate and differentiate at an air-liquid interface on a dermal equivalent support. Normal keratinocytes stratify and fully differentiate in a manner similar to the normal squamous epithelial tissues, while human papillomavirus-immortalized and established squamous carcinoma cell 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 factor-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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cancer Vaccines / isolation & purification
Cancer Vaccines / pharmacology
Carcinoma, Squamous Cell / immunology
Carcinoma, Squamous Cell / pathology
Carcinoma, Squamous Cell / prevention & control
Cell Line, Transformed
Cell Transformation, Viral
Dendritic Cells / immunology
Dendritic Cells / pathology
Epithelium / immunology
Epithelium / pathology
Humans
Immunity, Mucosal
Immunotherapy / methods*
In Vitro Techniques
Interferon-gamma / pharmacology
Keratinocytes / immunology*
Keratinocytes / virology
Models, Biological
Mucous Membrane / immunology
Mucous Membrane / pathology
Papillomaviridae / genetics
Papillomaviridae / immunology*
Papillomavirus Infections / immunology
Papillomavirus Infections / prevention & control
Precancerous Conditions / immunology
Precancerous Conditions / pathology
Precancerous Conditions / prevention & control
Recombinant Proteins
Tumor Necrosis Factor-alpha / pharmacology
Tumor Virus Infections / immunology
Tumor Virus Infections / prevention & control

Substances

Cancer Vaccines
Recombinant Proteins
Tumor Necrosis Factor-alpha
Interferon-gamma