5, 6 The expression of Foxp3 and IL-10 has been demonstrated in several carcinoma tissues and cultured cancer cell lines, suggesting that cancer ITF2357 solubility dmso cells themselves induce the Treg cell–like immunoregulatory milieu to evade immunosurveillance.7-10. Major histocompatibility complex

class II (MHC-II)–positive cells lacking the costimulatory molecules CD80 (B7-1) and CD86 (B7-2) induce anergy to native T cells. Among T cell subsets, Treg type 1 cells characterized by the production of IL-10 are induced by immature dendritic cells (DCs).11 Moreover, costimulation-dependent T cell clones stimulated without provision of the costimulatory signal were demonstrated not to be proliferative, but to differentiate into IL-10–producing anergic T cells in primary biliary cirrhosis.12 In addition to immunocompetent cells such as DCs, nonimmunocompetent cells, including carcinoma and normal epithelial cells,

have been demonstrated to express MHC-II, indicating an ability for antigen presentation, but these MHC-II–positive epithelial cells are usually called nonprofessional antigen-presenting selleck kinase inhibitor cells (APCs), differing from professional APCs such as DCs. Several studies have suggested that antigen presentation by MHC-II–positive epithelial cells that lack costimulation signals, such as keratinocytes and pancreatic islet cells, would favor the generation of anergic T cells.13-15 It is clinicopathologically important, but practically difficult, to differentiate between IgG4-related sclerosing cholangitis and extrahepatic cholangiocarcinoma. In this study, we retrospectively evaluated IgG4-positive plasma cells in extrahepatic cholangiocarcinomas

and mechanisms in terms of cholangiocarcinoma cells as nonprofessional APCs and regulatory cells. This study should help to clarify the pathological significance of IgG4 reactions in cholangiocarcinomas and also IgG4-related diseases. APC, antigen-presenting cell; DC, dendritic cell; ELISA, enzyme-linked immunosorbent assay; HPF, high-power field; IgG4, immunoglobulin G4; IL, interleukin; MHC-II, major histocompatibility complex class II; mRNA, messenger RNA; PCR, polymerase chain reaction; RT-PCR, reverse-transcription MCE polymerase chain reaction; Treg, regulatory T cell. Formalin-fixed and paraffin-embedded sections of 54 surgically resected specimens from 24 gallbladder cancers, 22 common bile duct cancers, and eight cancers of the Papilla of Vater (29 men, 25 women; average age, 74 years) were obtained from the registry of liver diseases in the Department of Pathology, Kanazawa University School of Medicine. Each cholangiocarcinoma was classified histologically as a well-differentiated (including papillary), moderately differentiated, or poorly differentiated adenocarcinoma based on the predominant histological grade.