TIE2-expressing monocytes and M2-polarized macrophages impact survival and correlate with angiogenesis in adenocarcinoma of the pancreas

Oncotarget. 2018 Jul 3;9(51):29715-29726. doi: 10.18632/oncotarget.25690.

Abstract

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.

Keywords: M2-macrophages; TIE2-expressing monocytes; angiogenesis; pancreatic adenocarcinoma; tumor-associated macrophages.