Leuk Lymphoma. 2013 May 20. [Epub ahead of print]
Upregulated expression of indoleamine 2,3-dioxygenase 1 in non-Hodgkin's lymphoma correlates with increase of infiltrated regulatory T cells.
Liu XQ, Lu K, Feng LL, Ding M, Gao JM, Ge XL, Wang X.
Indoleamine 2,3-dioxygenase 1 (IDO1), which is a key enzyme in the tryptophan metabolism expressed in some subsets of normal and neoplastic cells, participates in tumor-induced tolerance. However, the mechanisms involved are not clearly understood. A hypothesis suggests that IDO1 may be involved in proliferation and conversion of regulatory T cells (Tregs). In this study, we evaluated the levels of IDO and Forkhead box P3 (FoxP3) in non-Hodgkin's lymphoma (NHL) tissues and performed ex vivo experiments to investigate the role of IDO1 on T-cell tolerance in NHL. The results showed that expressions of IDO1 mRNA and proteins were coincidentally higher in NHL tissues than reactive hyperplasia of lymph node tissues. Up-regulation of IDO1 was correlated with later clinical phases, larger tumors and higher serum LDH, and indicated a worse prognosis. FoxP3 mRNA and protein levels were markedly increased alongside elevated IDO1 levels. Co-culture of murine CD4+CD25- T cells with A20 cells could initiate the conversion of CD4+CD25+ T cells which showed suppressive function in mixed lymphocyte reaction. Moreover, the potent inhibitor of IDO1, 1-methyl-L-tryptophan attenuated the conversion of CD4+CD25- T cells into CD4+CD25+FoxP3+ T cells. The results suggested that up-regulation of IDO1 in NHL tissues could induce local immune tolerance by favoring development and infiltration of FoxP3+ Tregs through the conversion of CD4+CD25- T cells into CD4+CD25+FoxP3+ T cells in the tumor microenvironment. This could be a novel mechanism of NHL escape from immune control. |
