Tumor-associated macrophages: Orchestrators of the tumor microenvironment

Macrophages are critical cellular mediators within the innate immune system and are the central effectors of chronic inflammation at the cellular level. Here, macrophages regulate the ongoing, simultaneous processes of tissue inflammation, destruction, and repair. They also play an integral role in recruiting key cell types within the inflammatory and wound healing response. Cancer is a chronic inflammatory state and largely considered a wound that does not heal. As in wound healing, where macrophages engulf and/or destroy foreign insults, macrophages have the potential to also eliminate tumor cells. However, it is now well known that these early pro-inflammatory, anti-tumor responses by macrophages are nullified as macrophages repolarize into pro-tumor, anti-inflammatory tumor-associated macrophages (TAMs) in response to tumor cell and microenvironmental-derived factors. After this point, TAMs drive neoplastic progression in multiple distinct ways. This indirect control of tumor progression, where TAMs share great functional overlap with the direct control elicited by neoplastic cells, supports TAMs being central orchestrators and later conductors of the tumor microenvironment (TME) – the focus of our review.