CTLA4 and melanoma: The mouse model we used lacks this mutational load as it is not induced by UV irradiation as human melanoma, but by the deliberate introduction of two genetic alterations, namely loss of Pten and gain of mutant Braf. As a result, the tumors induced in this model are probably less immunogenic than tumors arising in melanoma patients, likely explaining the absence of responses upon treatment with CTLA-4, PD-1 mAbs, IL-2 alone (Fig. 3) or in combination with targeted agents [26].