Elusive Identities and Overlapping Phenotypes of Proangiogenic Myeloid Cells in Tumors

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 identifyingand thus being able to target-this proangiogenic force in tumors. (Am J Pathol

The biology of personalized cancer medicine: Facing individual complexities underlying hallmark capabilities

“…Furthermore, studies in mouse models of cancer have revealed that profuse myeloid cell infiltration correlates with resistance to antiangiogenic therapies targeting the VEGF‐signaling axis (Bergers and Hanahan, 2008; Ferrara, 2010; Squadrito and De Palma, 2011), or accelerated tumor re‐growth following local tumor irradiation (Ahn and Brown, 2008; Kioi et al., 2010; Kozin et al., 2010). Additionally, there is considerable phenotypic and functional heterogeneity among macrophage and neutrophil subtypes, most simply reflected in the amalgam of conventionally or alternatively activated macrophages found in tumors, as well as in inflamed or healing tissues (Biswas and Mantovani, 2010; Coffelt et al., 2010; Gordon and Martinez, 2010; Nucera et al., 2011; Piccard et al., 2011). While less advanced in regard to appreciating individual variability, one can envision that the abundance and characteristics of these and other types of inflammatory cells will indeed prove to be deterministic and hence important parameters for personalized diagnosis.…”

Emerging paradigms and questions on pro-angiogenic bone marrow-derived myelomonocytic cells

“…While many studies have analyzed the role of TAM, MDSC and TEM in tumor angiogenesis, additional myeloid-derived cell populations may also contribute to this process, including neutrophils, eosinophils, mast cells and dendritic cells (DC) (Coffelt et al, 2010). For some of these cells, the mechanism by which they mediate or modulate tumor angiogenesis has been addressed, and in part elucidated, while for others it remains elusive.…”

“…Other types of cells, including neutrophils, eosinophils or dendritic cells may also express many of these markers and are reported to promote tumor angiogenesis (Coffelt et al, 2010;Murdoch et al, 2008) …”

“…Depending of their activating stimuli, recruited BMD and inflammatory cells may have anti-tumor or tumor promoting effects. Several different BMD cell populations contributing to tumor angiogenesis have been characterized (Coffelt et al, 2010;Murdoch et al, 2008). i) Endothelial cell progenitors, which incorporate into the vasculature and differentiate into mature endothelial cells.…”

“…Macrophages present in the tumor microenvironment are referred to as tumor associated macrophages or TAM (Coffelt et al, 2010;Mantovani et al, 2008;Murdoch et al, 2008) (Fig. 1).…”