Upon screening for possible TLR ligands, we selected the TLR7 agonist (TLR7A) imiquimod as it has been used in the clinics for the treatment of nonmelanoma skin cancer but also melanoma.28, 29, 30, 36 Furthermore, TLR7A has pleiotropic effects on T and NK cells and induces autophagic cell death in melanoma cells.37, 38 Moreover, a recent study showed that a novel TLR7A reversed NK cell anergy and induced antitumor CD8+ T cell responses.26, 27 Therefore, we assessed if treatment with a TLR7A as an immune modulator would be efficient in prolonging sensitivity to BRAFi. This evidence concerns the gene CD8A and melanoma.