In this regard, even the results reported by Snyder and colleagues in the context of advanced melanoma treated with CTLA-4 blockade demonstrated that a high mutational burden providing a greater likelihood of the development of specific tumor neo-antigens, recognized by the T-cells, is associated with a long-term clinical benefit from CTLA-4 blockade; conversely the absence of mutation-derived neo-antigens is associated with a minimal benefit or no benefit [54, 55]. This evidence concerns the gene CTLA4 and melanoma.