Redefining macrophage and neutrophil biology in the metastatic cascade.

Tumor cells metastasize to distant organs through a complex series of events that are driven by tumor intrinsic and extrinsic factors. In particular, non-malignant stromal cells, including immune cells, modify tumor metastatic behavior. Of these cells, tumor-associated innate immune cells, particularly macrophages and neutrophils, suppress the cytotoxic activity of innate and adaptive killer cells and interact with tumor cells to promote their growth and malignancy. These findings in mouse cancer models suggest that targeting these sub-populations of immune cells holds therapeutic promise in treating metastatic disease. In this review, we describe the origin and role of the macrophages, neutrophils, and their progenitors in the metastatic cascade and suggest strategies that might enhance cancer therapy.