In a separate study evaluating combination immunotherapies in a B16F10 melanoma model, it was noted that anti-PD-1/4-1BB combination efficiently induced a synergistic anti-tumor response, evidenced by robust CD8+/Treg ratios and the upregulation of anti-tumor response genes (CD3ε, CD8α, IFN-γ, Eomes), but with toxicity related to the anti-4-1BB antibody alone [101]. This evidence concerns the gene EOMES and neoplasm.