Indoleamine 2,3-dioxygenase Affects the Aggressiveness of Intraductal Papillary Mucinous Neoplasms Through Foxp3+CD4+CD25+ T Cells in Peripheral Blood


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Abstract

ObjectiveIntraductal papillary mucinous neoplasms (IPMNs) have a high malignant potential. We previously reported that peripheral Foxp3+CD4+CD25+ T-cell (Foxp3+ Treg) populations significantly increase with IPMN pathological aggressiveness. Dendritic cell-mediated induction of active Tregs from naive CD4+ T cells requires indoleamine 2,3-dioxygenase (IDO). Here, we evaluated whether an IDO–Foxp3+ Treg interaction plays a role in IPMN pathological aggressiveness.MethodsWe evaluated peripheral blood samples and resected specimens from 12 patients with IPMN. We analyzed Foxp3+CD4+CD25+ T cells in peripheral blood by fluorescence-activated cell sorting, evaluated the resected specimens by anti-IDO antibody staining, and compared them with the patients’ clinicopathological factors.ResultsThe pathological aggressiveness of IPMN was significantly associated with the number of peripheral Foxp3+ Tregs (P < 0.05) and IDO-positive cells per high-power field (HPF) (P < 0.01). There was a significant correlation between the numbers of peripheral Foxp3+ Tregs and IDO-positive cells/HPF (r = 0.625, P < 0.01). Patients with 7 or more IDO-positive cells/HPF had a significantly higher recurrence rate than those with less than 7 IDO-positive cells/HPF (P < 0.01, log-rank test).ConclusionsPeripheral Foxp3+ Tregs accurately reflect the aggressiveness of IPMNs. An increase in Foxp3+ Tregs can be induced by local IDO-positive cells in IPMN.

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