Context-dependent regulation of cutaneous immunological responses by TGFβ1 and its role in skin carcinogenesis

Transforming growth factor β1 (TGFβ1) signaling plays a critical role in skin carcinogenesis. While most studies have focused on TGFβ1 signaling and response in keratinocytes, it is now becoming clear that the interaction of keratinocyte-derived TGFβ1 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 TGFβ1 on tumor development. Indeed, the paradigm of TGFβ1 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 TGFβ1 on carcinogenesis in the skin and other epithelial tissues.