For example, depletion of tryptophan bioavailability in the tumor microenvironment triggers control non-derepressible 2 (GCN2)-mediated T-cell apoptosis [48] and attenuates T-cell proliferation, whereas increased accumulation of its downstream catabolite, kynurenine, promotes immune tolerance by inhibiting proliferation of T cells and natural killer cells and increasing proliferation of Tregs and myeloid derived suppressor cells [49,50]. This evidence concerns the gene EIF2AK4 and neoplasm.