Metastasis is the development of secondary tumors at a distance from a primary site of cancer (Figure 1). Metastatic cancer is a leading cause of death and significantly impacts on human health and society.

Metastasis in cancer cells is regulated by a complex interplay with noncancerous cells within the tumor microenvironment (Figure 2). These interactions are regulated at a number of levels, including direct cell–cell communication, binding of extracellular matrix components and secreted factors, such as cytokines

Immune cells in the tumor microenvironment called tumor-associated macrophages (TAMs) have emerged as major regulators of cancer disease progression. Cancer-associated fibroblasts (CAFs) are the most numerous noncancer cell type in tumors and regulate TAM differentiation from infiltrating monocyte cells.

Our research characterizes this three-way interplay of cancer cells, TAMs, and CAFs in promoting tumor progression. We are especially focused on identifying the inducible factors that communicate this process. Our studies provide a comprehensive understanding of the major driving forces underlying macrophage function within the tumor microenvironment and also benefits the development of therapeutics for patients with cancer.