CTLA4 and melanoma: Intratumoral injection of MEDI9197 (3M-052) (specific for TLR7/TLR8) induced macrophage repolarization and tumor regression in a mouse model of subcutaneous melanoma; a mechanism mediated by macrophages induced direct tumor cell killing via NO production and synergized with checkpoint inhibitors anti-CTLA4 and anti-PD-1 antibodies to inhibit tumor growth (269, 270).