Tumor-associated macrophages: A molecular perspective

The "macrophage balance hypothesis" was proposed in the early 1990s to depict the complex relationship that tumor-associated macrophages (TAM) have with the neoplastic cells of the tumor. TAM represent a prominent component of the mononuclear leukocyte population of solid tumors, which displays an ambivalent relationship with tumors. They originate in the circulation and are recruited to the tumor site by tumor-derived attractants such as chemokines and interact with the tumor cells and preferentially localize at the tumor-host tissue interface, in regions often associated with low oxygen tensions. The tumor microenvironment, including cytokines and hypoxia, regulates the localization and function of TAM. Emerging evidence starts to define the molecular basis for the peculiar functional phenotype of TAM and identifies possible therapeutic targets.