Based on the preliminary results achieved by agonist of TLR9 in metastatic melanoma, a phase-3 study (IMO-2125) is ongoing while the experimental arm is exploring the effect of Tilsotolimod in combination with ipilimumab in restoring the immunostimulatory activity, the DC activation, the CD8+ cell proliferation as well as a potential abscopal effect (81). This evidence concerns the gene TLR9 and metastatic melanoma.