The first successful approach of ICI has been the use of anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors in metastatic melanoma [25,27,28,29,30], and continuing with blocking the interactions between program cell death 1 (PD-1) and its ligands: program cell death ligand 1 (PDL-1) and program cell death ligand 2 (PDL-2) [25,27,28,29,30]. Here, CTLA4 is linked to metastatic melanoma.