Effect of Indoleamine 2, 3-dioxygenase on Dendritic Cell Co-stimulatory Molecules and Cytotoxic T Lymphocyte-mediated Cytolysis of Cancer Cells

Abstract

Increasing indoleamine 2,3-dioxygenase (IDO) produced by dendritic cells (DCs) in cancer patients results in immune response inhibition, leading to a spread of cancer cells. This study aimed to address the effect of IDO on phenotype of dendritic cells. Human monocyte- derived DCs obtained from 6 normal blood donors were cultured in vitro. The cultured DCs were tested for intracellular IDO expression by flow cytometry. In immature DCs, intracellular IDO was detected at minimal level but the level was increased when stimulated with lipopolysaccharide (LPS). After co-culture of monocyte-derived DCs with MCF-7 breast cancer cell line, the IDO was increased while the co-stimulatory molecules: HLA-DR and CD83 were decreased. Interestingly, the restoration of co-stimulatory molecules was detected after inhibition of IDO activity with 1-methyl-tryptophan (1-MT) and their ability to increase T cell cytotoxic activity against MCF-7 cells was demonstrated (p < 0.005, paired t-test). The study suggested that regulation of dendritic cells via IDO production could possibly induce the immune response for effective cytolysis of cancer cells.