In 2010, targeting CTLA-4 pioneered checkpoint blockade-based immunotherapy by improving the survival of patients with metastatic melanoma.213 A year after the publication of the clinical trial, anti-CTLA-4 immunotherapy was approved by the FDA for advanced melanoma, paving the way for targeting of other checkpoint receptors such as PD-1 in 2014. Here, PDCD1 is linked to metastatic melanoma.