Leveraging macrophage metabolism for anticancer therapy: opportunities and pitfalls

Tumor-associated macrophages (TAMs) constitute an important part of the tumor microenvironment (TME) that regulates tumor progression. Tumor-derived signals, hypoxia, and competition for nutrients influence TAMs to reprogram their cellular metabolism. This altered metabolic profile creates a symbiotic communication between tumor and other immune cells to support tumor growth. In addition, the metabolic profile of TAMs regulates the expression of immune checkpoint molecules. The dynamic plasticity also allows TAMs to reshape their metabolism in response to modern therapeutic strategies. Therefore, over the years, a significant number of approaches have been implicated to reprogram cancer-promoting metabolism in TAMs. In this review, we discuss the current strategies and pitfalls, along with upcoming promising opportunities in leveraging TAM metabolism for developing better therapeutic approaches against cancer.