Efficacy of levo-1-methyl tryptophan and dextro-1-methyl tryptophan in reversing indoleamine-2,3-dioxygenase-mediated arrest of T-cell proliferation in human epithelial ovarian cancer

Feng Qian, Jeannine Villella, Paul K. Wallace, Paulette Mhawech-Fauceglia, Joseph D. Tario, Christopher Andrews, Junko Matsuzaki, Danila Valmori, Maha Ayyoub, Peter J. Frederick, Amy Beck, Jianqun Liao, Richard Cheney, Kirsten Moysich, Shashikant Lele, Protul Shrikant, Lloyd J. Old, Kunle Odunsi

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

It has been reported that levo-1-methyl tryptophan (L-1MT) can block indoleamine-2,3-dioxygenase (IDO) expressed by human dendritic cells (DC), whereas dextro-1-methyl tryptophan (D-1MT) is inefficient. However, whether L-1MT or D-1MT can efficiently reverse IDO-induced arrest of human T-cell proliferation has not been clarified. Here, we show a marked immunosuppressive effect of IDO derived from INDO-transfected 293 cell, IDO+ ovarian cancer cells, and monocyte-derived DCs on CD4+ Th1 cells, CD8 + T cells, and natural killer cells derived from peripheral blood, ascites, and tumors of ovarian cancer patients. We found that, whereas L-1MT and D/L-1MT can restore proliferation of tumor-derived and peripheral blood T-cell subsets, D-1MT does not effectively restore IDO-induced arrest of T-cell proliferation. Although D-1MT inhibited kynurenine production at high concentrations, L-1MT was more effective in abrogating kynurenine generation and tryptophan depletion, whereas tryptophan was completely depleted by IDO even in the presence of high amounts of D-1MT. Together, the results indicate that, whereas the generation of tryptophan metabolites (kynurenines) by IDO is important in mediating suppression of T-cell proliferation, the degree to which tryptophan depletion is restored by 1MT is also critical in overcoming IDO-induced arrest of T-cell proliferation.

Original languageEnglish (US)
Pages (from-to)5498-5504
Number of pages7
JournalCancer research
Volume69
Issue number13
DOIs
StatePublished - Jul 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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