Inflammatory cells are a vital component of the
tumor stroma and, of these, tumor-associated macrophages (TAM) are the major cell type. TAMs are recruited early in
tumorigenesis and generally promote
metastasis, stimulate
tumor angiogenesis, and drive immunosuppression. TAMs have been shown to express the endothelial cell markers that enable chemotaxis and proangiogenic capacity. In this issue of
Cancer Research, Jakab and colleagues challenge the functional significance of Tie2-expressing monocytes/macrophages (TEM) in the context of
tumor growth and progression. By employing myeloid-specific deletion of the
angiopoietin receptor Tie2 and comprehensive analysis of myeloid cell single-cell
RNA sequencing datasets, they provide compelling data that Tie2-positive macrophages do not contribute to
tumor angiogenesis or relapse after
chemotherapy, two major biologic processes previously attributed to
tumor-associated TEMs. The study highlights that the concept of macrophage-expressed Tie2 as a therapeutic target or prognostic
indicator needs reconsideration. See related article by Jakab et al., p. 1353.