Classical and alternative activation of mononuclear phagocytes: picking the best of both worlds for tumor promotion

Abstract

Mononuclear phagocytes often function as control switches of the immune system, securing the balance between pro- and anti-inflammatory reactions. For this purpose and depending on the activating stimuli, these cells can develop into different subsets: classically (M1) or alternatively (M2) activated mononuclear phagocytes, the molecular and functional characterization of which is a current topic of investigation. Accumulating evidence suggests that cells of the monocyte/macrophage lineage can be hijacked by tumors for their own benefit. Either as immature cells in the periphery, or as mature macrophages at the tumor site, mononuclear phagocytes are able to influence the behavior of cancer cells, shape the tumor microenvironment and subvert anti-tumor immunity, thereby contributing to tumor growth and progression. This review focuses on the mechanisms behind monocyte/macrophage-mediated tumor promotion and interprets the available data within the M1/M2 conceptual frame.