FOXP3+ regulatory T cells and tumoral indoleamine 2,3-dioxygenase expression predicts the carcinogenesis of intraductal papillary mucinous neoplasms of the pancreas.
OBJECTIVE
FOXP3+ regulatory T cells (Tregs) play a central role in self-tolerance and suppress the effective antitumor immune response. A recent study revealed that indoleamine 2,3-dioxygenase (IDO)-mediated tryptophan depletion was able to affect local tumor-infiltrating lymphocytes. The aim of this study was to investigate the clinical significance of the tumor-infiltrating Tregs and tumoral IDO expression during the progression of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.


METHODS
We investigated the prevalence and localization of FOXP3+ Tregs, CD8+ lymphocytes, and IDO expression in IPMNs by immunohistochemistry. We recruited 39 cases with IPMNs (IPMA: adenoma, n = 11; IPMB: borderline malignancy, n = 9; IPMC: noninvasive carcinoma, n = 7; I-IPMC: invasive IPMC, n = 12).


RESULTS
The prevalence of Tregs increased step by step during the carcinogenesis of IPMNs (Kruskal-Wallis test: p < 0.0001). IDO expression in the tumor was observed in 5 cases with IPMNs (IPMC, n = 1; I-IPMC, n = 4). IDO expression in the tumor was positively correlated with the prevalence of Tregs in IPMNs.


CONCLUSIONS
FOXP3+ Tregs play a role in controlling the immune surveillance against IPMNs at the premalignant stage. IDO expression in the tumor is one of the late-stage phenomena of multistage carcinogenesis of IPMNs.
Gastroenterology Division, Yokohama City University Graduate School of Medicine, Yokohama, Japan. norikoba@yokohama-cu.ac.jp
Noritoshi
N
Kobayashi
Kensuke
K
Kubota
Shingo
S
Kato
Seitaro
S
Watanabe
Takeshi
T
Shimamura
Hiroyuki
H
Kirikoshi
Satoru
S
Saito
Michio
M
Ueda
Itaru
I
Endo
Yoshiaki
Y
Inayama
Shin
S
Maeda
Atsushi
A
Nakajima
D002288:Adenocarcinoma, Mucinous / Q000401:mortality / Q000473:pathology*; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007564:Japan / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000473:pathology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase