Clinical role of regulatory T cell in intraductal papillary mucinous neoplasms

Abstract

e15537 Background: Intraductal papillary mucinous neoplasms of pancreas (IPMNs) have malignant potential and exhibit a broad histologic spectrum, ranging from adenoma to invasive carcinoma. Recently, several investigators have reported that regulatory T cells (Foxp3+CD4+ T cells including CD4+CD25+ T cells and CD4+CD25- T cells) play important roles in anti-tumor immunity. We previously reported clinical role of increased populations of Foxp3+CD4+ T cells (Treg) in peripheral blood from advanced pancreatic cancer patients (Pancreas 2006). This study was conducted to clarify the clinical role of Treg for surveillance of IPMNs. Methods: Thirty-five patients with IPMNs (IPMC: n=8, IPMB: n=2, IPMA: n=5) and pancreas cancer (n=20) who underwent surgical resection were included in this study. Peripheral blood was withdrawn from IPMN patients (IPMC: n=5, IPMA: n=2) and PC patients (n=20), as well as healthy volunteer donors (n=20) as controls. The peripheral blood mononuclear cells (PBMCs) were subjected to FACScan analysis after labeling with anti-CD4, anti-CD25, and anti-Foxp3 antibodies. Immunohistochemical expression of Foxp3 (abcam: FOXP3 antibody, 236A/E7), Fascin (Dako: Fascin antibody, 55K-2) and TGF-β (Santa Cruz: TGF-β1 antibody, SC146) in main tumor was assessed in all IPMN patients. Results: The Treg population among the PBMCs was significantly increased in IPMC patients (median: 4.50%) and PC patients (median: 3.06%) compared with healthy donors (median: 1.30%). No significant difference in the Treg population among the PBMCs was observed between IPMC and PC patients. On the other hand, in IPMA patients (n=2), the Treg population among the PBMCs was equivarent to healthy donors (2.40 and 1.85% respectively). In immnohistochemical staining, the positive expression of Foxp3 was 87.5% (7 of 8) in IPMC patients, while in IPMA and IPMB patients, the expression of Foxp3 was not observed. The expression of Fascin and TGF-β was not correlated to malignant potential of IPMNs Conclusions: Increase of Foxp3+CD4+ T cells in the PBMCs is a new promising marker for malignant potential in IPMNs patients. No significant financial relationships to disclose.