Fig. 7: Identification of protein markers of response to immunotherapy in the melanomas.

a The heatmap showed clinical information of the anti-PD-1 cohort (n = 27). b The heatmap illustrated the immune signatures based on analysis using xCell. c Immunohistochemistry of CD8 in the responders and non-responders, scale bar = 100 μm. d The boxplot showed the xCell score of CD8⁺ T-cells in the responders and non-responders in Harel et al.’ cohort⁶² (n = 116) and Beck et al.’ cohort⁶³ (n = 185) (Wilcoxon rank test). e The histogram showed the biological pathways upregulated in responders and non-responders. f The heatmap showed the kinases whose kinase activity upregulated in responders and non-responders (n = 16). g The volcano plot showed the chemokines whose protein expression was significantly correlated with the kinase activity of MAPK7. h The volcano plot showed the chemokines whose protein expression was significantly correlated with the protein expression of NFKB2. i The workflow showed the sample collection for MS analysis. j Heatmap illustrated the protein expression of chemokines in the A375 cells under different treatment conditions. k The workflow showed the sample collection for enzyme-linked immunospot (ELISPOT) assay. l The histogram showed the concentration of IFN in the supernatant of A375 cells cultures with T cells under different treatment conditions, including MAPK7-overexpression, WT, MAPK7-siRNA, and MAPK7-inhibitor. The data represent the mean values ± SD (n = 3). m The boxplot showed the protein expression of PRKDC in the responders and non-responders in our cohort (n = 27) and Harel et al.’ cohort⁶² (n = 116) (Wilcoxon rank test). n Spearman-rank correlation of the MAPK7’s protein expression and PRKDC’s protein expression in melanomas. o The histogram showed the concentration of IFN in the supernatant of A375 cells cultures with T cells under different treatment conditions (KD-Ctrl-A375 cells, MAPK7-KD-A375 cells, KD-Ctrl-A375 cells treated with PRKDC inhibitor, MAPK7-KD-A375 cells treated with PRKDC inhibitor (NU7441)). The data represented the mean values ± SD (n = 3). p Tumor growth curves (n = 3 replicates per group) (mean ± SEM). q Boxplots indicated the protein expression of CCL5, CCL4, and CXCL4 between KD-MAPK7-A375 tumors and KD-Ctrl-A375 tumors. r Tumor growth curves (n = 3 replicates per group) (mean ± SEM).