Transfection of CD40 in a human oral squamous cell carcinoma keratinocyte line upregulates immune potency and costimulatory molecules

• Published in: British journal of dermatology (1951) Vol. 154; no. 2; pp. 231 - 238
• Main Authors: Villarroel Dorrego, M., Whawell, S.A., Speight, P.M., Barrett, A.W.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.02.2006; Blackwell; Oxford University Press
• Subjects: Antigens, CD - metabolism; Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Biological and medical sciences; Blotting, Western; Carcinoma, Squamous Cell - immunology; CD40 Antigens - genetics; CD40 Antigens - immunology; Cell Proliferation; Coculture Techniques; costimulatory molecules; Dermatology; Flow Cytometry; Histocompatibility Antigens Class II - metabolism; Humans; Immunophenotyping; Keratinocytes - immunology; Lymphocyte Activation - immunology; Medical sciences; Mouth Neoplasms - immunology; oral mucosal immunity; Otorhinolaryngology. Stomatology; squamous cell carcinoma; Transfection; Tumor Cells, Cultured; Tumors; Up-Regulation - immunology; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Human; oral mucosal immunity; Stomatology; Dermatology; Major histocompatibility system; Malignant tumor; Oral squamous cell carcinoma; Cell line; Transfection; T-Lymphocyte; costimulatory molecules; Keratinocyte; Oral cavity disease; squamous cell carcinoma
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2005.07006.x

Summary Background  There is upregulation of class II molecules of the major histocompatibility complex (MHC) by keratinocytes in oral squamous cell carcinoma (OSCC) and inflammatory diseases such as lichen planus. The significance of this expression, or whether it is accompanied by upregulation of membrane‐bound costimulatory molecules, is unknown. Objectives  To compare the expression of CD40, CD80, CD86, MHC class II and intercellular adhesion molecule‐1 (ICAM‐1), and the ability to induce allogeneic T‐lymphocyte proliferation in vitro, of a CD40– OSCC cell line, its CD40+ transfected derivative and null transfectants. Methods  OSCC cell lines and purified T lymphocytes were cocultured and T cell proliferation recorded. Phenotypes were analysed by flow cytometry. Results  After T lymphocyte proliferation, which all OSCC cell lines were able to induce, there was upregulation of MHC class II and ICAM‐1. However, the CD40+ transfectants were the most immunologically potent and were the only cells to show increased expression of CD86 (as well as further upregulation of CD40 and a statistically insignificant rise in CD80). The effects of blocking antibodies on T‐cell proliferation were only statistically significant with the CD40+ transfectants. Conclusions  While not essential, expression of CD40 by OSCC cells is necessary for optimal induction of allogeneic T lymphocytes, possibly because of concurrent upregulation of other membrane‐bound costimulatory molecules.