The canonical pathways (PD-L1/PD-1 pathway, the broader repertoire of checkpoint molecules active in melanoma brain metastasis, etc.)involved in the immune tolerance observed in melanoma BM have been repeatedly demonstrated to exist in human samples and specific in vitro/in vivo melanoma models of the brain and thus can be considered as having high confidence as causal contributors to CNS immune suppression [155]. Here, CD274 is linked to melanoma.