Figure 1. Keratinocyte-derived TSLP promotes growth and metastasis of Braf/Pten melanoma.

(A–C) Epidermal TSLP expression is induced during melanomagenesis in Braf/Pten mice. (A) Ear and ear-draining lymph nodes (ELN) appearance of Tyr:Cre^ERT2(tg/0) Braf^{LSL–V600E/+} Pten^lox/lox mice injected i.p. with tamoxifen (Braf/Pten mice). (B) Kinetic of TSLP protein levels in ears (left panel) and dorsal melanoma (right panel) from Braf/Pten mice, compared with ears and dorsal skin from control (CT, Tamoxifen-injected Tyr:Cre^ERT2(0/0) Braf^{LSL–V600E/+} Pten^lox/lox) littermates. Data are shown as mean ± SEM. n = 5 for all groups, except n = 4 for Braf/Pten dorsal tumors and CT dorsal skin at D49. (C) RNAScope ISH for TSLP mRNA on paraffin sections. Black arrows point to one of the positive signals in the epidermis (in red). Scale bar: 50 μm. (D–I) Ablation of TSLP delays melanoma growth and metastasis. (D) Ear appearance of Braf/Pten/Tslp^+/+ and Braf/Pten/Tslp^–/– mice at D30 and D35 following topical 4-hydroxytamoxifen (4-HT) treatment. (E and F) H&E staining (E) and IHC staining of SOX10 (F) of sections from ears at D30. Blue arrows points to one of the positive signals (in dark red). Scale bar: 50 μm. (G) Comparison of volumes of solid tumors developed in mice at the indicated time points. Data are shown as mean ± SEM. Student’s t test. **P < 0.01. n = 11 (Braf/Pten/Tslp^+/+) and n = 10 (Braf/Pten/Tslp^–/–). (H) Appearance of ELNs and dorsal tumor-draining inguinal lymph nodes (ILNs) at D41. (I) IHC staining of Sox10 on ILN sections at D41. Blue arrow points to one of the positive signals (in dark red). Scale bar: 50 μm. Data are representative of 3 independent experiments with similar results.