Elusive Identities and Overlapping Phenotypes of Proangiogenic Myeloid Cells in Tumors

Medical School, University of Sheffield, Sheffield, S10 2RX, UK.
American Journal Of Pathology (Impact Factor: 4.6). 02/2010; 176(4):1564-76. DOI: 10.2353/ajpath.2010.090786
Source: PubMed

ABSTRACT It is now established that bone marrow-derived myeloid cells regulate tumor angiogenesis. This was originally inferred from studies of human tumor biopsies in which a positive correlation was seen between the number of tumor-infiltrating myeloid cells, such as macrophages and neutrophils, and tumor microvessel density. However, unequivocal evidence was only provided once mouse models were used to examine the effects on tumor angiogenesis by genetically or pharmacologically targeting myeloid cells. Since then, identifying the exact myeloid cell types involved in this process has proved challenging because of myeloid cell heterogeneity and the expression of overlapping phenotypic markers in tumors. As a result, investigators often simply refer to them now as "bone marrow-derived myeloid cells." Here we review the findings of various attempts to phenotype the myeloid cells involved and discuss the therapeutic implications of correctly identifying-and thus being able to target-this proangiogenic force in tumors.

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Available from: Seth Coffelt, Nov 05, 2014
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    • "Tumors also recruit a variety of immature myeloid cells, often referred to as myeloid-derived suppressor cells (MDSCs), which comprise precursors of both the monocyte-DC (mononuclear ) and neutrophil (granulocytic) lineages and are commonly identified by their expression of Gr1 (Ly6C/G) and immunosuppressive activity. Mononuclear MDSCs can further mature into TAMs (Coffelt et al., 2010; Gabrilovich et al., 2012). Finally, there is also evidence for hematopoietic and myeloid progenitor cells homing to tumors and modulating tumor progression (Shaked and Voest, 2009). "
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    • "This complexity is reflected in the wide spectrum of infiltrating macrophages found in tumors that differ functionally and molecularly according to location within the tumor and local cues they encounter there [54] [55]. Making matters more complicated , myeloid cell types in tumors are highly related, can express similar markers, and in some instances perform similar functions [38]. Past studies in humans using CD68 as the sole marker of macrophages were not able to distinguish these subsets and it is now common to phenotype based on 2-3 different markers. "
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    • "This complexity is reflected by the heterogeneity of tumor-associated mononuclear phagocytes, both at the level of differentiation and activation. Distinguishing these different myeloid cell types in tumors is not always trivial, as they are highly related, often express similar markers and are in some cases able to perform similar functions (Coffelt et al. 2010a). In this respect, tumors are not different from any other tissue, where the identity of mononuclear phagocytes is not always unequivocal and the phenotype of these cells depends on parameters such as steady-state versus inflammation , type of inflammation, lymphoid organs versus non-lymphoid organs, and so on (Geissmann et al. 2010a). "
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