Major histocompatibility complex class II (MHC II) molecules, which are highly expressed in cutaneous melanomas [25], represent the canonical ligands of LAG-3, as they do for CD4, however, the proline-rich D1 domain allows LAG-3 to bind with higher affinity to MHC II than to CD4 [26–28]. This evidence concerns the gene LAG3 and cutaneous melanoma.