Diverse Functions of Macrophages in Different Tumor Microenvironments

Tumor-associated macrophages are a major constituent of malignant tumors and are known to stimulate key steps in tumor progression. In our review in this journal in 2006, we postulated that functionally distinct subsets of these cells exist in different areas within solid tumors. Here, we review the many experimental and clinical studies conducted since then to investigate the function(s), regulation, and clinical significance of macrophages in these sites. The latter include three sites of cancer cell invasion, tumor nests, the tumor stroma, and areas close to, or distant from, the tumor vasculature. A more complete understanding of macrophage diversity in tumors could lead to the development of more selective therapies to restore the formidable, anticancer functions of these cells. Cancer Res; 78(19); 5492-503. ©2018 AACR.