Tumor-Associated Macrophages in Tumor Progression: From Bench to Bedside

Abstract

Cancer-related inflammation is known to be a key determinant in cancer behavior, playing a pivotal role in cancer initiation and progression. Tumor-associated macrophages (TAM) represent the major leukocyte population among the tumor-infiltrating immune cells and display important and peculiar features. Within the tumor microenvironment, TAM may modulate their phenotype in response to distinct signals, resulting in a strict relationship with tumor cells. This plasticity confers the capability to change their behavior and reprogram their functions according to physiological or pathological situations. From a simplistic point of view, macrophages may be classified in M1 classical and M2 alternative macrophages, the latter displaying an immunomodulatory phenotype. M1 and M2 macrophages take part in different processes, such as resistance against pathogens and antitumor immunity or defense against parasites and resolution of inflammation, respectively. However, in addition to these, a number of functional diverse polarization states have been described. Several evidences indicate that in many tumors, macrophages display phenotypic and functional aspects that resemble M2 cells, which overall promote tumor initiation and progression. However, heterogeneity exists among TAM. In this scenario, TAM represent a possible target to improve anticancer therapy.