title: The PD-1/PD-L1 axis may be aberrantly activated in occupational cholangiocarcinoma.
abstract: An outbreak of cholangiocarcinoma in a printing company was reported in Japan, and these cases were regarded as an occupational disease (occupational cholangiocarcinoma). This study examined the expression status of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in occupational cholangiocarcinoma. Immunostaining of PD-1, PD-L1, CD3, CD8, and CD163 was performed using tissue sections of occupational cholangiocarcinoma (n = 10), and the results were compared with those of control cases consisting of intrahepatic (n = 23) and extrahepatic (n = 45) cholangiocarcinoma. Carcinoma cells expressed PD-L1 in all cases of occupational cholangiocarcinoma, whereas the detection of PD-L1 expression in cholangiocarcinoma cells was limited to a low number of cases (less than 10%) in the control subjects. In cases of occupational cholangiocarcinoma, occasional PD-L1 expression was also noted in precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct. Additionally, tumor-associated macrophages and tumor-infiltrating T cells expressed PD-L1 and PD-1, respectively. The number of PD-L1-positive mononuclear cells, PD-1-positive lymphocytes, and CD8-positive lymphocytes infiltrating within the tumor was significantly higher in occupational cholangiocarcinoma compared with that in control cases. These results indicate that immune escape via the PD-1/PD-L1 axis may be occurring in occupational cholangiocarcinoma.
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shigekazu
authors.initials: S
authors.lastname: Takemura
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Genya
authors.initials: G
authors.lastname: Hamano
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, National Hospital Organization, Osaka National Hospital, Osaka, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Nakamori
authors.affiliation: Department of Surgery, Nissay Hospital, Osaka, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fujikawa
authors.affiliation: Artificial Organ & Transplantation Division, Department of Surgery, University of Tokyo, Tokyo, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sugawara
authors.affiliation: Department of Surgery, Ishikiriseiki Hospital, Higashiosaka, Japan.
authors.forename: Takatsugu
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka Red Cross Hospital, Osaka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Arimoto
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Yamamura
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.affiliation: Department of Diagnostic Pathology, Fukui-ken Saiseikai Hospital, Fukui, Japan.
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
authors.affiliation: Department of Hepato-Biliary-Pancreatic Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Kubo
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D060890:B7-H1 Antigen / Q000032:analysis / Q000096:biosynthesis*; D001650:Bile Duct Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D018281:Cholangiocarcinoma / Q000139:chemically induced / Q000276:immunology / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007564:Japan; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D016273:Occupational Exposure / Q000009:adverse effects; D011230:Precancerous Conditions / Q000473:pathology; D011327:Printing; D061026:Programmed Cell Death 1 Receptor / Q000032:analysis / Q000096:biosynthesis*; D012997:Solvents / Q000009:adverse effects
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012997:Solvents
keywords: immune escape; multistep carcinogenesis; occupational cholangiocarcinoma; organic solvent exposure