The role of p53 in the immunobiology of cutaneous squamous cell carcinoma

Abstract

SUMMARYCutaneous squamous cell carcinoma is typically characterized by the over-expression of the tumour suppressor protein p53. Considerable evidence suggests that immune competence is important in the control of cutaneous SCC. We discuss the immunobiology of p53 and its relevance to cutaneous SCC, including the potential interaction with human papillomavirus.

Impaired Notch Signaling Promotes De novo Squamous Cell Carcinoma Formation

“…Insights into the molecular pathogenesis of cutaneous SCC are slowly emerging (17,40,41). Previous studies have shown that loss of nuclear factor nB (NF-nB) activity, through enhanced InB expression, or depletion of SMAD4 in murine skin confers susceptibility to SCC, in part, through promotion of unbalanced keratinocyte proliferation (41)(42)(43)(44)(45)(46).…”

Oral squamous papilloma: clinical, histologic and immunohistochemical analyses

“…The viruses considered to be of high oncogenic potential include HPVs 16,18,31,33,35,39,45,51,55,56,58,59, 66 and 68 (5), and these have been associated with the development of various types of human neoplasias, particularly lesions of epithelial cells of the uterine cervix, urethra, anogenital region, skin, digestive tract, tracheal/bronchial and nasal mucosa and oral mucosa (6,7). DNA sequences of HPV 16 and 18 are found in approximately 85% of invasive squamous cell carcinomas and their precursors, such as grave dysplasia and carcinoma in situ.…”

Genomics of Basal and Squamous Cell Carcinomas

“…Research into immune response to p53 had led to promising therapeutic potential. p53-specific cytotoxic T lymphocytes capable of mediating protective immunity to tumours have been generated in murine models (Black et al, 2003,Clin Exp Immunol.). Adoptive transfer of p53 specific cytotoxic T lymphocytes generated in p53-/-mice confers immunity on the recipient to p53 overexpressing murine tumour (Vierboom et al, 1997,J Exp Med.).…”

“…Following viral genome integration, E6 and E7 oncoproteins are overexpressed, with inhibition of apoptosis via p53 dependent and independent mechanisms (Thomas et al, 1999, Oncogene). E6 protein from the cervical associated HPC-16 mediates degradation of p53 (Black et al, 2003,Clin Exp Immunol). A common p53 polymorphism at position 72 replacing proline with arginine renders p53 more susceptible to E6 mediated degradation.…”

“…Adoptive transfer of p53 specific cytotoxic T lymphocytes generated in p53-/-mice confers immunity on the recipient to p53 overexpressing murine tumour (Vierboom et al, 1997,J Exp Med.). As p53 is over expressed in cutaneous SCC, vaccination against p53 is a logical approach to induce tumour reactive immunity (Black et al , 2003,Clin Exp Immunol.) Vaccines used to induce p53 specific immune responses in mice have included, Canary pox virus vectors (Roth et al, 1996,Proc Natl Acad Sci U S A.…”