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

Georgi Atanasov,Georg Wiltberger,Gabriela Aust,Marcus Bahra,Moritz Schmelzle,Michael Bartels,Charlotte Pötner,Andreas Pascher,Felix Krenzien,Corinna Dietel,Uwe Eichfeld,Katrin Schierle,Christian Benzing

doi:10.18632/oncotarget.25690

Abstract

IntroductionM2-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).ResultsPatients 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).ConclusionsPresence of M2-polarized TAMs and TEMs is associated with a decreased overall and recurrence-free survival of patients with PDAC.Materials and methodsThe 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.

Highlights

M2-polarized tumor-associated macrophages (TAMs) and TIE2expressing monocytes (TEMs) are associated with angiogenesis and have been identified as a potential prognostic marker in several solid tumors, including hepatobiliary malignancies
Patients with tumors characterized by the presence of CD163+ TAMs or TEMs in tumor central area (TCA) or tumor invasive front (TIF), respectively, showed a significantly decreased 1, 3- and 5-year overall and recurrence-free survival compared to patients without CD163+ TAMs or TEMs
Patients with TEMs in TCA showed a higher incidence of tumor recurrence (ρ < 0.05)

Summary

Introduction

M2-polarized tumor-associated macrophages (TAMs) and TIE2expressing monocytes (TEMs) are associated with angiogenesis and have been identified as a potential prognostic marker in several solid tumors, including hepatobiliary malignancies. Solid cancers harbor different subpopulations of immune cells, each of which has the potential for pro- or anti-tumor functions. The immune activation state of these tumor-associated macrophages (TAMs) can be divided into M1- (anti-cancer function) and M2-type (pro-tumoral or immunosuppressive) [2]. Various escape mechanisms deployed by malignant cells and the tumor microenvironment (TME) mediate the conversion of infiltrating macrophages into immunosuppressive and pro-tumoral M2 TAMs [3]. As previously reported by us, a differential influence and functionality of localized tumor sites in TME, i.e. tumor central area (TCA) and tumor invasive front (TIF), on related immunologic responses play a key role in cancer immunity and tumor progression [4]. A constant interplay between immune responses in TCA or TIF and infiltrating TAMs and their polarization states, plays a key role in this process

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