Transcriptional profiling of public melanoma data sets revealed that ISG15 is most highly expressed by macrophages in the TME (Supplementary Figure 8A), that ISG15 expression is positively associated with expression of checkpoint molecules PD-1, PD-L1, and CTLA4 (Supplementary Figure 8B), and that high tumor expression of ISG15 is associated with reduced objective response rate (ORR) with a trend for reduced overall survival (OS) (Supplementary Figure 8C). Here, CTLA4 is linked to neoplasm.