STAT6 inhibition induces cell-cycle arrest in MF and SS tumor cells. (A-C) Heat maps showing examples of downregulated pathways after STAT6 inhibition for 48 hours in blood HC (n = 3) and SS (n = 4) CD4⁺ T cells and MF skin tumor (n = 3) samples. DEGs after STAT6 inhibition are shown in comparison with untreated. (D) Cytometry analysis of the cell cycle of SS CD4⁺ T cells treated with/without AS1517499 for 48 hours. A representative example showing different phases of the cell cycle. (E) Measured cell-cycle phase distribution shown as a percentage. Data are represented as mean ± standard deviation of 5 independent SS samples (P < .001). (F) Single-cell transcriptomes of 3672 CD3⁺ cells (256 cells from normal [n = 4] and 3416 cells from MF [n = 3] skin samples, color coded by subject) clustered using Seurat³⁸  (supplemental Figure 4). (G) Transcriptomes of TOX⁺ T lymphocytes from patient tumors and healthy control skin samples. (H) Dot-plot showing the proportion of cells and the scaled average gene expression of the STAT-6-regulated genes identified in panels A-C in MF and healthy skin samples determined by scRNAseq. (I) Double-color immunofluorescence microscopy of ex vivo skin explants cultured as in Figure 2D-E and stained for PCNA/TOX, CDK2/TOX, and CCNE2/TOX, as indicated, at ×1000. 4′,6-diamidino-2-phenylindole stains nuclei. Representative examples are shown.