IDO2 and neoplasm: proposed several potential reasons for the negative outcome of using epacadostat plus immunotherapy in metastatic melanoma (56), such as insufficient IDO1 inhibition by epacadostat in the tumor; no selection of patients for tumoral IDO1 expression; no selection for patients refractory to immunotherapy; the adaptivity of the IDO1 expression mechanism in melanoma; compensatory expression of tryptophan dioxygenase or IDO2; the activation of the AhR by epacadostat, which drives immune suppression; and the insufficient blockade of the tryptophan–Kyn–AhR pathway by IDO1 inhibitors (56).