Indoleamine 2,3-dioxygenase (IDO) metabolizes tryptophan to kynurenine, leading to the production of NAD
+ via the kynurenine pathway. The overexpression of IDO in tumors and tumor-draining lymph nodes induces immune tolerance and enhances tumor growth
in vivo.
1,2 1-methyl-D-Tryptophan is an inhibitor of IDO (IC
50 = 7 μM) that is effective
in vivo.
3,4 In mice, 1-methyl-D-tryptophan prevents T-cell anergy triggered by dendritic cells overexpressing IDO.
4 It augments the antitumor and antiviral immunoresponse of CD8
+ T-cells and reduces tumor volume in mice with xenografts overexpressing IDO.
1,2 1-methyl-D-Tryptophan, in combination with chemotherapy, causes regression of tumors and prolongs survival.
1,5 Surprisingly, 1-methyl-D-tryptophan induces the expression of IDO in human ovarian carcinoma SKOV3 cells in culture.
5