These results are consistent with early studies by Riley et al. showing that ICOS expression can be blunted by CTLA-4 engagement [35], and more recently studies by Allison’s group have showed that CTLA-4 blockade combined with a tumor cell vaccine engineered to express ICOS ligand significantly enhanced tumor-specific CD8+ T cell responses and improve tumor clearance in a B16 melanoma model [40]. This evidence concerns the gene CD8A and melanoma.