Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock

Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer

Abstract

Tumour-infiltrating myeloid cells, including tumour-associated macrophages (TAMs), have been implicated in tumour progression. We recently described a lineage of mouse monocytes characterised by expression of the Tie2 angiopoietin receptor and required for the vascularization and growth of several tumour models. Here, we report that TIE2 expression in human blood identifies a subset of monocytes distinct from classical inflammatory monocytes and comprised within the less abundant "resident" population. These TIE2-expressing monocytes (TEMs) accounted for 2-7% of blood mononuclear cells in normal donors and were distinct from rare circulating endothelial cells and progenitors. In human cancer patients, TEMs were observed in the blood and, intriguingly, within the tumours, where they represented the main monocyte population distinct from TAMs. Conversely, TEMs were hardly detected in non-neoplastic tissues. In vitro, TEMs migrated towards Angiopoietin-2, a TIE2 ligand released by activated endothelial cells and angiogenic vessels, suggesting a homing mechanism for TEMs to tumours. Purified human TEMs, but not TEM-depleted monocytes, markedly promoted angiogenesis in xenotransplanted human tumours, suggesting a potentially critical role of TEMs in human cancer progression. Human TEMs may provide a novel, biologically relevant marker of angiogenesis and represent a previously unrecognized target of cancer therapy.