Elevated Epidermal Thymic Stromal Lymphopoietin Levels Establish an Antitumor Environment in the Skin

SummaryThymic Stromal Lymphopoietin (TSLP), a cytokine implicated in induction of T helper 2 (Th2)-mediated allergic inflammation, has recently been shown to stimulate solid tumor growth and metastasis. Conversely, studying mice with clonal loss of Notch signaling in their skin revealed that high levels of TSLP released by barrier-defective skin caused a severe inflammation, resulting in gradual elimination of Notch-deficient epidermal clones and resistance to skin tumorigenesis. We found CD4+ T cells to be both required and sufficient to mediate these effects of TSLP. Importantly, TSLP overexpression in wild-type skin also caused resistance to tumorigenesis, confirming that TSLP functions as a tumor suppressor in the skin.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (322 K)Download as PowerPoint slideHighlights► RBPj-deficient skin with severe Th2 inflammation is resistant to tumorigenesis ► TSLP signaling is responsible for tumor resistance in Notch-signaling deficient skin ► TSLP acts through CD4+ T cells to establish tumor resistance ► Induction of TSLP in wild-type skin can produce resistance to tumorigenesis