FOXP3+ regulatory T cells and tumoral indoleamine 2,3-dioxygenase expression predicts the carcinogenesis of intraductal papillary mucinous neoplasms of the pancreas.

BACKGROUND AND AIMS

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.