Targeting monocytes/macrophages in fibrosis and cancer diseases: Therapeutic approaches

Over almost 140 years since their identification, the knowledge about macrophages has unbelievably evolved. The 'big eaters' from being thought of as simple phagocytic cells have been recognized as master regulators in immunity, homeostasis, healing/repair and organ development. Long considered to originate exclusively from bone marrow-derived circulating monocytes, macrophages have been also demonstrated to be the first immune cells colonizing tissues in the developing embryo and persisting in adult life by self-renewal, as long-lived tissue resident macrophages. Therefore, heterogeneous populations of macrophages with different ontogeny and functions co-exist in tissues. Macrophages act as sentinels of homeostasis and are intrinsically programmed to lead the wound healing and repair processes that occur after injury. However, in certain pathological circumstances macrophages get dysfunctional, and impaired or aberrant macrophage activities become key features of diseases. For instance, in both fibrosis and cancer, that have been defined 'wounds that do not heal', dysfunctional monocyte-derived macrophages overall play a key detrimental role. On the other hand, due to their plasticity these cells can be 're-educated' and exert anti-fibrotic and anti-cancer functions. Therefore macrophages represent an important therapeutic target in both fibrosis and cancer diseases. The current review will illustrate new insights into the role of monocytes/macrophages in these devastating diseases and summarize new therapeutic strategies and applications of macrophage-targeted drug development in their clinical setting.