TSLP mediated inflammation influence cancer

© 2012 EPFL

© 2012 EPFL

Loss of Cutaneous TSLP-Dependent Immune Responses Skews the Balance of Inflammation from Tumor Protective to Tumor Promoting.

"Inflammation can promote or inhibit cancer progression. In this study, the group of Freddy Radtke (ISREC UPRAD) 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, they 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."

See: Matteo Di Piazza, Craig S. Nowell, Ute Koch, André-Dante Durham, Freddy Radtke. Cancer Cell, Volume 22, Issue 4, 479-493, 10.1016/j.ccr.2012.08.016 (2012)