Indoleamine 2,3-dioxygenase affects the aggressiveness of intraductal papillary mucinous neoplasms through Foxp3+CD4+CD25+ T cells in peripheral blood.
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.
Department of Digestive and Transplant Surgery, Institute of Health Bioscience Graduate School of Medicine, The University of Tokushima, Tokushima, Japan. tikemoto@clin.med.tokushima-u.ac.jp
Tetsuya
T
Ikemoto
Mitsuo
M
Shimada
Masato
M
Komatsu
Shinichiro
S
Yamada
Yu
Y
Saito
Hiroki
H
Mori
Yuji
Y
Morine
Satoru
S
Imura
Yoshimi
Y
Bando
Tohru
T
Utsunomiya
D002288:Adenocarcinoma, Mucinous / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D000231:Adenocarcinoma, Papillary / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000276:immunology / Q000556:secondary / Q000601:surgery; D002469:Cell Separation / Q000379:methods; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000097:blood*; D006801:Humans; D007150:Immunohistochemistry; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000032:analysis*; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000276:immunology / Q000473:pathology / Q000601:surgery; D050378:T-Lymphocytes, Regulatory / Q000201:enzymology* / Q000276:immunology; D016896:Treatment Outcome
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D053645:Interleukin-2 Receptor alpha Subunit