The generation, activation, and polarization of monocyte-derived macrophages in human malignancies

Macrophages are immune cells that originate from embryogenesis or from the differentiation of monocytes. They can adopt numerous phenotypes depending on their origin, tissue distribution and in response to different stimuli and tissue environment. Thus, in vivo, macrophages are endowed with a continuum of phenotypes that are rarely strictly pro-inflammatory or anti-inflammatory and exhibit a broad expression profile that sweeps over the whole polarization spectrum. Schematically, three main macrophage subpopulations coexist in human tissues: naive macrophages also called M0, pro-inflammatory macrophages referred as M1 macrophages, and anti-inflammatory macrophages also known as M2 macrophages. Naive macrophages display phagocytic functions, recognize pathogenic agents, and rapidly undergo polarization towards pro or anti-inflammatory macrophages to acquire their full panel of functions. Pro-inflammatory macrophages are widely involved in inflammatory response, during which they exert anti-microbial and anti-tumoral functions. By contrast, anti-inflammatory macrophages are implicated in the resolution of inflammation, the phagocytosis of cell debris and tissue reparation following injuries. Macrophages also play important deleterious or beneficial roles in the initiation and progression of different pathophysiological settings including solid and hematopoietic cancers. A better understanding of the molecular mechanisms involved in the generation, activation and polarization of macrophages is a prerequisite for the development of new therapeutic strategies to modulate macrophages functions in pathological situations.

Automated summary

Macrophages can adopt various phenotypes and play important roles in immune response, inflammation, and tissue repair. In human tissues, there are three main subpopulations of macrophages: naive macrophages, pro-inflammatory macrophages, and anti-inflammatory macrophages. Naive macrophages display phagocytic functions and can polarize into pro or anti-inflammatory macrophages. Pro-inflammatory macrophages are involved in the inflammatory response, while anti-inflammatory macrophages aid in the resolution of inflammation and tissue repair. Understanding the molecular mechanisms of macrophage generation, activation, and polarization is crucial for developing new therapeutic strategies.