The roles of CSFs on the functional polarization of tumor-associated macrophages.

Macrophages have a central role in numerous physiological processes, such as immune defense, maintenance of tissue homeostasis, wound healing, and inflammation. Moreover, in numerous severe disorders, such as cancer or chronic inflammation, their functions can be profoundly affected. Macrophages continuously sense their environment and adapt their phenotypes and functions to the local requirements; this process is called plasticity. In addition to stress signals, metabolites, and direct cell-contact interactions with surrounding cells, numerous cytokines play a central role in controlling macrophage polarization. In this review, we will focus on three human macrophage differentiation factors: macrophage colony-stimulating factor (M-CSF), IL-34, and granulocyte M-CSF. These CSFs allow human monocyte survival, promote their differentiation into macrophages, and control macrophage polarization as they give rise to cells with different phenotype and functions. Based on recent observations, the role of granulocyte CSF on macrophage polarization is also addressed. Finally, our current knowledge on the expression of these growth factors in tumor microenvironment and their impact on the generation and polarization of tumor-associated macrophages are summarized.