Metabolism and TAM functions-it takes two to tango.

From the evidence on clinical studies and experimental mouse models we now know that tumor-associated macrophages (TAMs) sustain tumor development in many different ways. They play a role in angiogenesis, tumor cell invasion, and metastasis formation. Additionally, TAMs interfere with natural killer and T-cell antitumoral activities, producing an immune-suppressive environment that protects tumor cell growth. This indicates that the tumoricidal activity of macrophages within the tumor microenviroment is lost due to an imbalance of the regulatory mechanisms underpinning these cells' function. Since metabolism is emerging as a major modulator of macrophage function, metabolic changes in response to signals coming from cancer or other immune cells might promote this imbalance, enhancing the tumorigenic activities of TAMs. In this review we describe the novel, most recent findings on how metabolism shapes TAM functions or conversely, how TAMs influence the activity of other cells through metabolic mechanisms. The complete elucidation of the metabolic switches between pro- and antitumoral properties of macrophages, now still in its infancy, is destined to provide scientists with new instruments not only to understand but also to combat cancer.