Activation of the leukemia plasmacytoid dendritic cell line PMDC05 by Toho-1, a novel IDO inhibitor

Abstract

Background/aim: Indoleamine-2,3-dioxygenase (IDO) is a rate-limiting enzyme for tryptophan metabolism and plays an immunosuppressive role. Antigen-presenting cells, when activated, increase the expression of IDO, which results in the suppression of subsequent immune reaction. A novel IDO inhibitor, Toho-1, was explored for its applicability to immunotherapy.

Materials and methods: We investigated the effects of Toho-1 on antigen presentation and antigen-specific cytotoxic T-lymphocyte-inducing ability of leukemia plasmacytoid dendritic cell line PMDC05, which was established in our laboratory.

Results: While antigen presentation-associated molecules in PMDC05 cells were increased by stimulation with lipopolysaccharide and interferon-γ, IDO mRNA and protein expression were also enhanced. Such treatment of PMDC05 cells in combination with Toho-1 enhanced the antigen-presenting and CTL-inducing ability of PMDC05 cells.

Conclusion: These findings suggest the ability of Toho-1 to potentiate antigen-presenting cells and its applicability in immunotherapy of cancer.

Keywords: CTL-inducing ability; Necrostatin-1®; Novel IDO inhibitor; PMDC05; Toho-1; antigen-presenting ability; leukemic plasmacytoid dendritic cell line.