Indoleamine 2,3-dioxygenase Affects the Aggressiveness of Intraductal Papillary Mucinous Neoplasms Through Foxp3+CD4+CD25+ T Cells in Peripheral Blood
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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DOI：
10.1097/mpa.0b013e3182575e4a
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发表时间：
2013-01-01
期刊：
影响因子：
2.9
通讯作者：
Utsunomiya, Tohru
中科院分区：
文献类型：
--
作者：
Ikemoto, Tetsuya;Shimada, Mitsuo;Utsunomiya, Tohru
目的：导管内乳头状黏液性肿瘤（IPMNs）具有高度恶性潜能。我们先前报道了外周Foxp 3（+）CD 4（+）CD 25（+）T细胞（Foxp 3（+）Treg）群体随着IPMN病理侵袭性显著增加。树突状细胞介导的从初始CD 4（+）T细胞诱导活性TcR需要吲哚胺2，3-双加氧酶（IDO）。在此，我们评估IDO-Foxp 3（+）Treg相互作用是否在IPMN病理侵袭性中起作用。我们用荧光激活细胞分选法分析外周血Foxp 3（+）CD 4（+）CD 25（+）T细胞，用抗IDO抗体染色评估切除标本，并与患者的临床病理因素进行比较。IPMN的病理侵袭性与外周Foxp 3（+）T细胞数目显著相关每高倍视野IDO阳性细胞数（HPF）（P < 0.01）。外周血Foxp 3（+）T淋巴细胞数与IDO阳性细胞数/HPF呈显著正相关（r = 0.625，P < 0.01）。IDO阳性细胞数≥ 7个/HPF者复发率显著高于IDO阳性细胞数<7个/HPF者（P < 0.01）。Foxp 3（+）T细胞的增加可由IPMN中的局部IDO阳性细胞诱导。
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.