TIE2-expressing monocytes and M2-polarized macrophages impact survival and correlate with angiogenesis in adenocarcinoma of the pancreas
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Georgi Atanasov1,2,3,*, Charlotte Pötner1,*, Gabriela Aust4, Katrin Schierle5, Corinna Dietel1, Christian Benzing1,2, Felix Krenzien1,2,3, Michael Bartels1,6, Uwe Eichfeld1, Moritz Schmelzle1,2, Marcus Bahra2, Andreas Pascher2 and Georg Wiltberger1,7
1Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany
2Department of Surgery, Campus Charité Mitte und Campus Virchow-Klinikum, Charité, Universitätsmedizin Berlin, Berlin, Germany
3Berlin Institute of Health, Berlin, Germany
4Department of Surgery, Research Laboratories, University of Leipzig, Leipzig, Germany
5Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
6Department of General and Visceral Surgery, Helios Clinic Leipzig, Leipzig, Germany
7Department of General, Visceral and Transplantation Surgery, University Hospital of RWTH Aachen, Aachen, Germany
*These authors contributed equally to this work
Georgi Atanasov, email: email@example.com
Keywords: TIE2-expressing monocytes; pancreatic adenocarcinoma; tumor-associated macrophages; M2-macrophages; angiogenesis
Received: December 15, 2017 Accepted: June 12, 2018 Published: July 03, 2018
Introduction: M2-polarized tumor-associated macrophages (TAMs) and TIE2-expressing monocytes (TEMs) are associated with angiogenesis and have been identified as a potential prognostic marker in several solid tumors, including hepatobiliary malignancies. However, little is known regarding their influence on tumor progression and patient survival in pancreatic ductal adenocarcinoma (PDAC).
Results: Patients with tumors characterized by the presence of CD163+ TAMs or TEMs in TCA or TIF, respectively, showed a significantly decreased 1-, 3- and 5-year overall and recurrence-free survival compared to patients without CD163+ TAMs or TEMs (all ρ < 0.05). Patients with TEMs in TCA showed a higher incidence of tumor recurrence (ρ < 0.05). Furthermore, the presence of CD163+ TAMs was associated with a higher tumor MVD (ρ < 0.05).
Conclusions: Presence of M2-polarized TAMs and TEMs is associated with a decreased overall and recurrence-free survival of patients with PDAC.
Materials and methods: The localization and density of CD163+ M2-polarized TAMs and TEMs were quantified in the tumor central area (TCA) and tumor-infiltrating front (TIF) in human PDAC tissue (n = 106) and correlated to clinicopathological characteristics, tumor recurrence rates and patient survival. In parallel, tumor microvascular density (MVD) and the density of angiopoietin-positive tumor cells were quantified. Statistical analysis was performed using SPSS software.
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