Abstract
Simple SummaryTumors often include many immune cells that are theoretically able to combat tumor growth. Yet, tumors can induce immune functions that support tumor growth via different routes. In this review, we discuss how cancer cell metabolism regulates the activity of macrophages within tumors and how this affects tumor progression. This is particularly relevant as metabolic pathways in both cancer and immune cells can serve as targets to improve cancer treatment.Tumors consist of a wide variety of cells, including immune cells, that affect tumor progression. Macrophages are abundant innate immune cells in the tumor microenvironment (TME) and are crucial in regulating tumorigenicity. Specific metabolic conditions in the TME can alter the phenotype of tumor-associated macrophages (TAMs) in a direction that supports their pro-tumor functions. One of these conditions is the accumulation of metabolites, also known as oncometabolites. Interactions of oncometabolites with TAMs can promote a pro-tumorigenic phenotype, thereby sustaining cancer cell growth and decreasing the chance of eradication. This review focuses on the metabolic cancer-macrophage crosstalk in the TME. We discuss how cancer cell metabolism and oncometabolites affect macrophage phenotype and function, and conversely how macrophage metabolism can impact tumor progression. Lastly, we propose tumor-secreted exosome-mediated metabolic signaling as a potential factor in tumorigenesis. Insight in these processes may contribute to the development of novel cancer therapies.
Highlights
The tumor microenvironment (TME) harbors many components such as cancer cells, immune cells, fibroblasts, and endothelial cells
Tumors exhibit altered metabolism compared to normal tissues, preferring glycolysis over oxidative phosphorylation (OXPHOS) even in the presence of oxygen, a phenomenon known as the Warburg effect [20,21]
This has the advantage of providing both biosynthetic building blocks needed for proliferation and signaling intermediates that can affect the phenotype of cells present in the TME [21]
Summary
The tumor microenvironment (TME) harbors many components such as cancer cells, immune cells, fibroblasts, and endothelial cells. Fatty acid oxidation was thought to be crucial for this macrophage subtype; later glycolysis was recognized as an alternative pathway to fuel OXPHOS [15,18,19] Tumors can exploit this connection between immune cell metabolism and function to suppress immunity and to promote tumor progression. Tumors exhibit altered metabolism compared to normal tissues, preferring glycolysis over OXPHOS even in the presence of oxygen, a phenomenon known as the Warburg effect [20,21] This has the advantage of providing both biosynthetic building blocks needed for proliferation and signaling intermediates that can affect the phenotype of cells present in the TME [21].
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