Tumor-Associated Macrophages: Reasons to Be Cheerful, Reasons to Be Fearful.

Tumor microenvironment (TME) is a complex and constantly evolving entity that consists not only of cancer cells, but also of resident host cells and immune-infiltrating cells, among which macrophages are significant components, due to their diversity of functions through which they can influence the immune response against tumor cells. Macrophages present in tumor environment are termed as tumor-associated macrophages (TAMs). They are strongly plastic cells, and depending on the TME stimuli (i.e., cytokines, chemokines), TAMs polarize to antitumoral (M1-like TAMs) or protumoral (M2-like TAMs) phenotype. Both types of TAMs differ in the surface receptors' expression, activation of intracellular signaling pathways, and ability of production and various metabolites release. At the early stage of tumor formation, TAMs are M1-like phenotype, and they are able to eliminate tumor cells, i.e., by reactive oxygen species formation or by presentation of cancer antigens to other effector immune cells. However, during tumor progression, TAMs M2-like phenotype is dominating. They mainly contribute to angiogenesis, stromal remodeling, enhancement of tumor cells migration and invasion, and immunosuppression. This wide variety of TAMs' functions makes them an excellent subject for use in developing antitumor therapies which mainly is based on three strategies: TAMs' elimination, reprograming, or recruitment inhibition.