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expression and signaling of ICs in the tumor microenvironment. Recent findings on dual targeting of ICs and metabolic checkpoints have also been discussed.Treatment options for patients with metastatic melanoma have expanded rapidly since the approval of ipilimumab by the U.S. Food and Drug Administration in 2011. Cytokines such as interferon and interleukin-2 were approved in 1995 and 1998 respectively. However, the effect on survival was marginal, and the toxicity,