p53 Phosphorylation and TP53 Copy-Number Alterations in Chronic Graft-Versus-Host Oral Lichen Preceding Squamous Cell Carcinoma

Abstract

knockdown may have altered the immune surveillance milieu in the skin with its complex cytokine patterns and reduced numbers and function of Tregs, thereby leading to the increase of NER mechanisms and subsequent reduction of DNA damage as measured by CPDs (Figure 1c, d, and f). In addition, the CD28 ligands BB-1 and B7 that are expressed in keratinocytes provide an important co-stimulatory signal for CD3mediated proliferation of T lymphocytes, including alloreacting CD4 þ T cells (Koulova et al., 1991; Simon et al., 1994). This raises the possibility that T-cell activation by keratinocytes after UVB exposure may have been inhibited by in vivo CD28 siRNA knockdown. In this regard, it is interesting to note that functional blockade of CD80/CD86 significantly decreased UV-induced tumor development (Loser et al., 2005). In any case, further studies are warranted to determine the precise mechanisms by which CD28 knockdown leads to increased NER and decreased DNA damage and skin alterations.