Myeloid cells functioning in tumor vascularization as a novel therapeutic target

Angiogenesis, the sprouting of new blood vessels to sustain growth, is an important new target in solid tumor therapy. Initial studies focused on the role of the tumor cell in promoting angiogenesis; yet more recent work has demonstrated that host cells in the tumor microenvironment also play a critical role in tumor vascularization. Additionally, vasculogenesis in which new blood vessels develop from vascular progenitor cells also contributes to tumor growth. Recent studies propose a central role for cells of the myeloid lineage in triggering vessel growth by releasing angiogenic factors and perhaps by incorporating directly into nascent blood vessels. We will review studies that support a critical role for myeloid cells in neovascularization, with a focus on cells that express various monocytic/dendritic cell markers, including vascular leukocytes (VLCs), Tie2+ monocytes, and vascular endothelial growth factor receptor 2 (VEGFR2)+ monocytes, among others. The evidence that these myeloid cells represent bona fide therapeutic targets for solid tumors will be reviewed. Finally, we will address some controversies and challenges in the field with a focus on future directions.