[PDF][PDF] Loss of cutaneous TSLP-dependent immune responses skews the balance of inflammation from tumor protective to tumor promoting

M Di Piazza, CS Nowell, U Koch, AD Durham, F Radtke - Cancer cell, 2012 - cell.com
M Di Piazza, CS Nowell, U Koch, AD Durham, F Radtke
Cancer cell, 2012cell.com
Inflammation can promote or inhibit cancer progression. In this study we have addressed the
role of the proinflammatory cytokine thymic stromal lymphopoietin (TSLP) during skin
carcinogenesis. Using conditional loss-and gain-of-function mouse models for Notch and
Wnt signaling, respectively, we demonstrate that TSLP-mediated inflammation protects
against cutaneous carcinogenesis by acting directly on CD4 and CD8 T cells. Genetic
ablation of TSLP receptor (TSLPR) perturbs T-cell-mediated protection and results in the …
Summary
Inflammation can promote or inhibit cancer progression. In this study we have addressed the role of the proinflammatory cytokine thymic stromal lymphopoietin (TSLP) during skin carcinogenesis. Using conditional loss- and gain-of-function mouse models for Notch and Wnt signaling, respectively, we demonstrate that TSLP-mediated inflammation protects against cutaneous carcinogenesis by acting directly on CD4 and CD8 T cells. Genetic ablation of TSLP receptor (TSLPR) perturbs T-cell-mediated protection and results in the accumulation of CD11b+Gr1+ myeloid cells. These promote tumor growth by secreting Wnt ligands and augmenting β-catenin signaling in the neighboring epithelium. Epithelial specific ablation of β-catenin prevents both carcinogenesis and the accumulation of CD11b+Gr1+ myeloid cells, suggesting tumor cells initiate a feed-forward loop that induces protumorigenic inflammation.
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