The Role of Tumor-Associated Macrophages (TAMs) in Tumor Progression
Tumors are organ-like structures composed of neoplastic as well as non-malignant stroma cells. One of the most prominent cellular components of the tumor stroma are tumor-associated macrophages (TAMs). Pre-clinical as well as clinical studies have shown a
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The Role of Tumor-Associated Macrophages (TAMs) in Tumor Progression Astrid Schmieder and Kai Schledzewski
Abstract Tumors are organ-like structures composed of neoplastic as well as non-malignant stroma cells. One of the most prominent cellular components of the tumor stroma are tumor-associated macrophages (TAMs). Pre-clinical as well as clinical studies have shown an inversed correlation between macrophage infiltration and patients’ prognosis, indicating a macrophage supporting role for tumor progression. Macrophages are a heterogeneous cell population with many different functions for the organism. They have been broadly classified into pro-inflammatory, classically activated macrophages (M1; stimulated by IFN-γ or LPS) and anti-inflammatory, alternatively activated macrophages (M2; stimulated by either IL-4/IL-13, IL-1β/LPS in combination with immune complexes or by IL-10/β/glucocorticoids). TAMs have been shown to possess a M1-like phenotype in tumor initiation, while during tumor progression they acquire characteristics of M2-like macrophages. The latter TAMs support tumor growth by their pro-angiogenic, anti-inflammatory and matrix-remodeling abilities. They do so by secreting diverse growth factors like VEGF, PDGF, or EGF and chemokines and cytokines such as IL-10, TGF-β, CCL2, and CXCL12. In addition, they support tumor invasion by secreting matrix remodeling molecules such as matrix metalloproteinases (MMP) and cathepsins. These abilities qualify TAMs as important novel adjuvant therapeutic targets for human cancer. First approaches directed against tumor-promoting TAM populations as well as their functions with, for example, bisphosphonates have already shown some promising results.
A. Schmieder (*) • K. Schledzewski Department of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer Ufer 1-3, 68167 Mannheim, Germany e-mail: [email protected]; [email protected] M. Klink (ed.), Interaction of Immune and Cancer Cells, DOI 10.1007/978-3-7091-1300-4_3, © Springer-Verlag Wien 2014
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A. Schmieder and K. Schledzewski
List of Abbreviations AID ANG2 bFGF CCL CCR2 COX-2 CSF-1R CX3CR1 CXCL EGF EMT GM-CSF HGF HIF HPV IDO IFN-γ IL iNOS LPS M1 M2 M-CSF/CSF-1 MDSC MHC MIF MMP MMTV MPS MRC1 NF-κB PDGF PlGF PyVT ROS STAT3 TAM TEM TGF-β Th1 Th2 TLR
Activation-induced cytidine deaminase Angiopoietin-2 Basic fibroblast growth factor Chemokine (C–C motif) ligand CC-chemokine receptor 2 Cyclooxygenase-2 Colony-stimulating factor receptor 1 CX3C-chemokine receptor 1 CXC chemokine ligand Epidermal growth factor Epithelial–mesenchymal transition Granulocyte–macrophage colony-stimulating factor Hepatocyte growth factor Hypoxia-inducible factor Human papilloma virus Indoleamine dioxigenase Interferon γ Interleukin Inducible nitric oxide synthase. Lipopolysaccharide Classically activated macrophage Alternatively activated macrophage Macrophage colony-stimulating factor 1 Myeloid-derived suppressor cells Major histocompatibi
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