Double-crosser of the Immune System: Macrophages in Tumor Progression and Metastasis

Macrophages are the phagocytic sentinel cells of our body, with high plasticity required to maintain homeostasis. This incredibly diverse set of cells, in response to various environmental stimuli such as cytokines and other factors, constantly alters their functional state/phenotype. They undergo polarization not only into conventional M1/M2 axis but also undergo a diverse spectrum of macrophage subtypes which play critical roles in various immune functions and homeostasis. In the tumor microenvironment, monocytes polarize along with the alternatively activated macrophages AAM or M2 macrophages associated with pro-tumoral features whereas M1 macrophages exert antitumor functions. Tumor-Associated Macrophage (TAM) infiltration has long been associated with poor prognosis and therefore represents potential diagnostic and prognostic biomarkers in solid tumors. Inhibiting the recruitment of monocytes into the tumor microenvironment and targeted deletion of TAMs have shown promising results. Targeting the TAMs towards M1-like macrophages has also demonstrated to be an efficient way to prevent tumor progression and metastasis. Here in this article, we review how TAMs orchestrate different steps in tumor progression and metastasis and the opportunities to target them in the quest for cancer prevention and treatment. Further, we explore how chemotherapies and immunotherapies can target TAM reprogramming and depletion to serve as a strategy for the control of various types of cancers in the future.