The Cancer Cell Metabolic Reprogramming Remodels the Tumor Microenvironment: Molecular Mechanisms and Therapeutic Strategies

Abstract

ABSTRACT Metabolic reprogramming and immune evasion are two key mechanisms that facilitate tumor progression. Tumor cells achieve their energy requirements for rapid proliferation through metabolic reprogramming, such as glucose metabolism, lipid metabolism, and amino acid metabolism. Tumor cell metabolic reprogramming can influence immune cell function in the tumor microenvironment through various mechanisms, ultimately facilitating tumor immune escape. Targeting tumor cell metabolism and combining metabolic regulation with immunotherapy can enhance anti‐tumor immune cells, inhibit the function of immunosuppressive cells, improve anti‐tumor therapy, and overcome immune escape. This review elucidates the regulatory mechanisms by which glucose, lipids, amino acid metabolism, nucleotide metabolism, oxidative phosphorylation, lactate, and hypoxia modulate the proliferation, differentiation, and function of anti‐tumor immune cells and immunosuppressive cells. Regulatory strategies to restore the anti‐tumor function of immune cells in response to metabolic changes were discussed. These strategies are expected to improve the effect of immunotherapy and are used in combination with other treatments to provide new ideas for cancer management.