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

Abstract

Objective 

Intraductal 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.

Methods 

We 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.

Results 

The 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).

Conclusions 

Peripheral Foxp3⁺ Tregs accurately reflect the aggressiveness of IPMNs. An increase in Foxp3⁺ Tregs can be induced by local IDO-positive cells in IPMN.