Overexpression of B7-H1 on epidermal keratinocytes promotes squamous cell carcinoma formation. (87.28)

Abstract

Abstract B7-H1 is inducible in various tumor cells and inflammatory tissue cells. We established B7-H1 transgenic mice (Tg), which overexpressed B7-H1 in keratinocytes (KCs). KC-associated B7-H1 directly regulated effector CD8+ T cells at the local inflammatory sites in contact hypersensitivity. Malignant tumor-formation is closely correlated with inflammatory responses. In this study, we investigate the roles of KC-associated B7-H1 in MCA-induced squamous cell carcinoma (SCC) formation. Intradermal injection of MCA preferentially induces SCC. We compared histology and inflammatory status between control and B7-H1Tg mice. Seven days after MCA injection, control BALB/c mice showed severe inflammatory responses with rapid expansion of epidermal cells, more infiltrations in the dermis, and higher cytokine expression. In contrast, B7-H1Tg mice showed less infiltration and expansion of epidermal cells, and exhibited poor alignment and higher chromatin condensation in the basal cells. After 7 wks, B7-H1Tg showed significantly higher incidence of SCC. Our results demonstrated that overexpression of B7-H1 on KCs promotes SCC formation, although the B7-H1/PD-1-mediated interactions between infiltrated cells and epidermal cells regulates inflammatory responses at early time points. The exhibition of higher incidence of SCC in B7-H1Tg mice suggests intrinsic changes in epidermal KCs by B7-H1-transduction rather than PD-1-dependent action.