We show that a more potent TLR9 agonist (i.e. MGN1703 versus ODN1826) combined with a more potent CTLA-4 antibody (i.e. 9D9-mIgG2a versus 9H10) very significantly increased the therapeutic potential of this combination against bilateral, poorly immunogenic B16-F10 melanoma (0% versus 50% tumor-free survival). This evidence concerns the gene CTLA4 and melanoma.