CD73 expression in normal and pathological human hepatobiliopancreatic tissues

Autor: Stefano La Rosa, Laurence de Leval, Benoit Gilbert, Christophe Caux, Christine Sempoux, Christine Ménétrier-Caux, Nermin Halkic, Amedeo Sciarra, Pedro Romero, Inês Monteiro
Přispěvatelé: Lausanne University Hospital, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Université de Lausanne = University of Lausanne (UNIL), Manship, Brigitte
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Cancer Research
Carcinoma
Hepatocellular
Epithelial-Mesenchymal Transition
Hepatocellular carcinoma
medicine.medical_treatment
[SDV]Life Sciences [q-bio]
Immunology
GPI-Linked Proteins
Immune tolerance
CD73
Cholangiocarcinoma
Ecto-5′-nucleotidase
Immunohistochemistry
Pancreatic carcinoma
03 medical and health sciences
0302 clinical medicine
Cancer immunotherapy
medicine
Immunology and Allergy
Humans
Epithelial–mesenchymal transition
Biliary Tract
5'-Nucleotidase
Pancreas
business.industry
Liver Neoplasms
medicine.disease
Prognosis
3. Good health
Staining
[SDV] Life Sciences [q-bio]
Pancreatic Neoplasms
medicine.anatomical_structure
Oncology
Bile Duct Neoplasms
Liver
Biliary tract
5'-Nucleotidase/analysis
5'-Nucleotidase/antagonists & inhibitors
Bile Duct Neoplasms/chemistry
Bile Duct Neoplasms/mortality
Bile Duct Neoplasms/pathology
Biliary Tract/chemistry
Carcinoma
Hepatocellular/chemistry
Carcinoma
Hepatocellular/mortality
Carcinoma
Hepatocellular/pathology
Carcinoma
Pancreatic Ductal/chemistry
Carcinoma
Pancreatic Ductal/mortality
Carcinoma
Pancreatic Ductal/pathology
Cholangiocarcinoma/chemistry
Cholangiocarcinoma/mortality
Cholangiocarcinoma/pathology
GPI-Linked Proteins/analysis
GPI-Linked Proteins/antagonists & inhibitors
Liver/chemistry
Liver Neoplasms/chemistry
Liver Neoplasms/mortality
Liver Neoplasms/pathology
Pancreas/chemistry
Pancreatic Neoplasms/chemistry
Pancreatic Neoplasms/mortality
Pancreatic Neoplasms/pathology
Cancer research
business
030215 immunology
Carcinoma
Pancreatic Ductal
Zdroj: Cancer immunology, immunotherapy, vol. 68, no. 3, pp. 467-478
Cancer Immunology, Immunotherapy
Cancer Immunology, Immunotherapy, 2019, 68 (3), pp.467-478. ⟨10.1007/s00262-018-2290-1⟩
ISSN: 0340-7004
1432-0851
DOI: 10.1007/s00262-018-2290-1⟩
Popis: International audience; Background: The tumor-expressed CD73 ectonucleotidase generates immune tolerance and promotes invasiveness via adenosine production from degradation of AMP. While anti-CD73 blockade treatment is a promising tool in cancer immunotherapy, a characterization of CD73 expression in human hepatobiliopancreatic system is lacking.Patients and methods: CD73 expression was investigated by immunohistochemistry in a variety of non-neoplastic and neoplastic conditions of the liver, pancreas, and biliary tract.Results: CD73 was expressed in normal hepatobiliopancreatic tissues with subcellular-specific patterns of staining: canalicular in hepatocytes, and apical in cholangiocytes and pancreatic ducts. CD73 was present in all hepatocellular carcinoma (HCC), in all pancreatic ductal adenocarcinoma (PDAC), and in the majority of intra and extrahepatic cholangiocellular carcinomas, whereas it was detected only in a subset of pancreatic neuroendocrine neoplasms and almost absent in acinar cell carcinoma. In addition to the canonical pattern of staining, an aberrant membranous and/or cytoplasmic expression was observed in invasive lesions, especially in HCC and PDAC. These two entities were also characterized by a higher extent and intensity of staining as compared to other hepatobiliopancreatic neoplasms. In PDAC, aberrant CD73 expression was inversely correlated with differentiation (p < 0.01) and was helpful to identify isolated discohesive tumor cells. In addition, increased CD73 expression was associated with reduced overall survival (HR 1.013) and loss of E-Cadherin.Conclusions: Consistent CD73 expression supports the rationale for testing anti-CD73 therapies in patients with hepatobiliopancreatic malignancies. Specific patterns of expression could also be of help in the routine diagnostic workup.
Databáze: OpenAIRE
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