Tumoral immune resistance based on tryptophan degradation by indoleamine 2,3-dioxygenase

Abstract

Tumor cells constitutively express indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan and lowers tryptophan concentration in the local microenvironment. Such altered microenvironment protects tumor cells from rejection by the immune system, as T lymphocytes are exquisitely sensitive to tryptophan shortage. This may explain the low clinical efficacy of cancer immunotherapy based on vaccination. Preclinical studies indicate that this immune resistance mechanism can be blocked by systemic delivery of a pharmacological IDO inhibitor, 1-methyl-l-tryptophan. These results suggest the clinical efficacy of cancer immunotherapy can be boosted by combined treatment of cancer patients with an IDO inhibitor.