Abstract
Advances in immunotherapy have underscored the importance of antitumor immune responses in controlling cancer. However, the tumor microenvironment (TME) imposes several obstacles to the proper function of immune cells, including a metabolically challenging and immunosuppressive microenvironment. The increased metabolic activity of tumor cells can lead to the depletion of key nutrients required by immune cells and the accumulation of byproducts that hamper antitumor immunity. Furthermore, the presence of suppressive immune cells, such as regulatory T cells and myeloid-derived suppressor cells, and the expression of immune inhibitory receptors can negatively impact immune cell metabolism and function. This review summarizes the metabolic reprogramming that is characteristic of various immune cell subsets, discusses how the metabolism and function of immune cells are shaped by the TME, and highlights how therapeutic interventions aimed at improving the metabolic fitness of immune cells and alleviating the metabolic constraints in the TME can boost antitumor immunity.
Highlights
Altered metabolism is a hallmark of cancer, with many tumor cells skewing their metabolism toward aerobic glycolysis—a phenomenon known as the Warburg effect—to fuel the metabolic and biosynthetic demands of rapid cell proliferation
This review summarizes the metabolic reprogramming that is characteristic of various immune cell subsets, discusses how the metabolism and function of immune cells are shaped by the tumor microenvironment (TME), and highlights how therapeutic interventions aimed at improving the metabolic fitness of immune cells and alleviating the metabolic constraints in the TME can boost antitumor immunity
While these results provide tangible links between dietary status and protective antitumor immune responses, delineating cellintrinsic and -extrinsic mechanisms by which diet influences immune cell function will be essential in order to apply dietary interventions to cancer immunotherapy clinically
Summary
Altered metabolism is a hallmark of cancer, with many tumor cells skewing their metabolism toward aerobic glycolysis—a phenomenon known as the Warburg effect—to fuel the metabolic and biosynthetic demands of rapid cell proliferation. This increased metabolic activity can lead to the depletion of key nutrients and the accumulation of waste products within the tumor microenvironment (TME). These metabolic changes often impact the function of other cell types, immune cells, leading to dysregulated immune responses and decreased antitumor immunity. We discuss efforts to target immune cell metabolism for the purpose of increasing antitumor immune responses and improving the efficacy of cancer immunotherapies
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