Despite these intriguing potential mechanisms of immunoregulatory action, we failed to observe major changes in M2 TAM or Treg presence the TME of B16 tumors treated with ADU-S100 +/- blocking/neutralizing anti-ISG15 antibody, suggesting that ISG15 may mediate additional (as yet) undefined pro-tumor mechanisms in the B16 (but not BPR20) melanoma model. Here, ISG15 is linked to melanoma.