We uncovered an unexpected, and undesired, on-target effect of IDO1 inhibition: whereas IDO1 inhibitors were developed to protect cytotoxic T cells and other immune cells against the deleterious effects of TRP depletion in the TME, we demonstrate here that IDO1 inhibition (or TRP replenishment) also leads to protection of melanoma cells from T cell elimination in vitro and in vivo. Here, IDO1 is linked to melanoma.