Although initial results of IDO1 inhibition in clinical trials were encouraging,26,38–40 the recent phase III ECHO 301 trial testing epacadostat in combination with the PD-1 inhibitor pembrolizumab in melanoma did not show an improved outcome as compared to pembrolizumab alone.41 In the present study we found that epacadostat improved agonistic CD40 mAb therapy in B16-F10 tumors and enhanced T-cell activation, as evidenced by increased expression of CD69 and CD107a on CD8+ effector T-cells. This evidence concerns the gene CD69 and melanoma.