title: Increased levels of granulocytic myeloid-derived suppressor cells in peripheral blood and tumour tissue of pancreatic cancer patients.
abstract: Pancreatic cancer (PC) often presents late with poor survival. While role of immunosuppressive cells in preclinical studies provided help to develop immunotherapeutic agents, these cells remain under investigation in PC. The aim of this study was to characterise the different subsets of myeloid-derived suppressor cells (MDSCs) and evaluate their level and function in the circulation and tissue of PC patients. Significant increases in circulating and tumour-infiltrating granulocytic (Lin-HLA-DR-CD33+CD11b+CD15+), but not monocytic (Lin-HLA-DR-CD14+), MDSCs were detected in PC patients when compared with healthy donors and patients with chronic pancreatitis. The circulating MDSCs from PC patients expressed arginase 1, which represents their functional state. Blood levels of MDSCs showed no association with PC stage or preoperative levels of tumour markers. These findings provide a first characterisation of the phenotype of different subsets of peripheral and local MDSCs in PC patients and suggest that the frequency and contribution of these cells are predominantly granulocytic. This information demonstrates that MDSCs play a role in pancreatic cancer and future large validation studies may help in the development of new immunotherapeutic strategies to inhibit or eliminate MDSC function.
authors.affiliation: Institutes of Cancer, Inflammation & Repair, University of Manchester, Manchester M20 4BX, UK ; Biomedical Research Centre, School of Environment & Life Sciences, University of Salford, The Crescent, Peel Building, Manchester M5 4WT, UK ; Department of Upper Gastrointestinal Surgery, Salford Royal NHS Foundation Trust, Manchester M6 8HD, UK ; Department of Hepatobiliary Surgery, North Manchester General Hospital, Manchester M8 5RB, UK ; Section of Translational Anaesthetic and Surgical Sciences, Leeds Institute of Molecular Medicine, Leeds LS9 7TF, UK.
authors.forename: Yazan S
authors.initials: YS
authors.lastname: Khaled
authors.affiliation: Institutes of Cancer, Inflammation & Repair, University of Manchester, Manchester M20 4BX, UK ; Biomedical Research Centre, School of Environment & Life Sciences, University of Salford, The Crescent, Peel Building, Manchester M5 4WT, UK ; Department of Upper Gastrointestinal Surgery, Salford Royal NHS Foundation Trust, Manchester M6 8HD, UK ; Department of Hepatobiliary Surgery, North Manchester General Hospital, Manchester M8 5RB, UK.
authors.forename: Basil J
authors.initials: BJ
authors.lastname: Ammori
authors.affiliation: Institutes of Cancer, Inflammation & Repair, University of Manchester, Manchester M20 4BX, UK ; Biomedical Research Centre, School of Environment & Life Sciences, University of Salford, The Crescent, Peel Building, Manchester M5 4WT, UK ; College of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE.
authors.forename: Eyad
authors.initials: E
authors.lastname: Elkord
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001119:Arginase / Q000235:genetics / Q000276:immunology; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics* / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D050500:Pancreatitis, Chronic / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; D006684:HLA-DR Antigens; D009363:Neoplasm Proteins; C574619:ARG1 protein, human; D001119:Arginase
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