Using multiplex immunohistochemistry and spatial imaging analysis of paired tumor sections obtained from 11 melanoma patients prior to BRAF/MEK-targeted therapy and when the disease progressed on therapy, we observed a significant increase of tumor cellularity in the progressed tumors and the close association of SOX10+ melanoma cells with CD8+ T cells negatively correlated with patient’s progression-free survival (PFS). The gene discussed is SOX10; the disease is melanoma.