The PD‐1/PD‐L1 axis may be aberrantly activated in occupational cholangiocarcinoma

• Published in: Pathology international Vol. 67; no. 3; pp. 163 - 170
• Main Authors: Sato, Yasunori, Kinoshita, Masahiko, Takemura, Shigekazu, Tanaka, Shogo, Hamano, Genya, Nakamori, Shoji, Fujikawa, Masahiro, Sugawara, Yasuhiko, Yamamoto, Takatsugu, Arimoto, Akira, Yamamura, Minako, Sasaki, Motoko, Harada, Kenichi, Nakanuma, Yasuni, Kubo, Shoji
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01.03.2017
• Subjects: Aberration; Adult; Aged; Apoptosis; Apoptosis - physiology; B7-H1 Antigen - analysis; B7-H1 Antigen - biosynthesis; Bile; Bile Duct Neoplasms - chemically induced; Bile Duct Neoplasms - immunology; Bile Duct Neoplasms - pathology; Bile ducts; CD163 antigen; CD3 antigen; CD8 antigen; Cholangiocarcinoma; Cholangiocarcinoma - chemically induced; Cholangiocarcinoma - immunology; Cholangiocarcinoma - pathology; Female; Humans; immune escape; Immunohistochemistry; In Situ Nick-End Labeling; Japan; Lesions; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Macrophages; Male; Middle Aged; Mortality; multistep carcinogenesis; Neoplasia; occupational cholangiocarcinoma; Occupational diseases; Occupational Diseases - etiology; Occupational Diseases - immunology; Occupational Diseases - pathology; Occupational Exposure - adverse effects; organic solvent exposure; Outbreaks; PD-1 protein; PD-L1 protein; Precancerous Conditions - pathology; Printing; Programmed Cell Death 1 Receptor - analysis; Programmed Cell Death 1 Receptor - biosynthesis; Solvents - adverse effects; multistep carcinogenesis; immune escape; organic solvent exposure; occupational cholangiocarcinoma
• ISSN: 1320-5463; 1440-1827
• DOI: 10.1111/pin.12511

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.