Conversely, i.t. administration of ADU-S100 together with systemic oral delivery of ARG2i/COX2i/NOS2i (but not i.p. anti-PD-L1 or i.t. anti-ISG15) provided superior anti-tumor efficacy vs. ADU-S100 alone in the BPR20 (BRAFV600EPTEN-/-) melanoma model. This evidence concerns the gene ISG15 and melanoma.