CTLA4 and metastatic melanoma: Indeed, large randomized controlled trials on immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or programmed cell death protein-1 (PD-1) and its ligand (PD-L1) pathways consistently demonstrated clinical efficacy in, e.g., metastatic melanoma [14–16], non-small cell lung cancer [17–21], with typical response rates of 20–40 % that appeared to be durable [22].