Context-dependent regulation of cutaneous immunological responses by TGFbeta1 and its role in skin carcinogenesis.

Transforming growth factor beta1 (TGFbeta1) signaling plays a critical role in skin carcinogenesis. While most studies have focused on TGFbeta1 signaling and response in keratinocytes, it is now becoming clear that the interaction of keratinocyte-derived TGFbeta1 with cells of the immune system has an equally important role in tumor development. Tumors form within the context of innate and adaptive immune responses and studies in skin and skin carcinogenesis models have provided important insight into the impact of context-dependent pro-inflammatory and immunosuppressive actions of TGFbeta1 on tumor development. Indeed, the paradigm of TGFbeta1 duality is clearly evident in its ability to both promote and inhibit inflammatory responses. Recent studies have begun to shed new light on the molecular basis for these actions and to provide insight into how these may contribute to context-dependent effects of TGFbeta1 on carcinogenesis in the skin and other epithelial tissues.