Copy-number alterations (CNAs) of IFNGR1/IFGR2, IRF1, and interferon-receptor-associated Janus kinase 2(JAK2), as well as amplification of SOCS1 and PIAS4, have been identified in non-responders with metastatic melanoma patients through whole-exome sequencing (WES).127,128 Mutations of JAK1/2 and beta-2-microglobulin (B2M) have also been identified in PD-1 blockade resistant melanoma patients through WES.129,130 Abundant copy-number alterations, B2M loss, and phospholipase A2 group IID (PLA2G2D) overexpressed correspond with adaptive ICB resistance in another pan-cancer analysis.120. This evidence concerns the gene PDCD1 and metastatic melanoma.