Targeting Metabolic Reprogramming in Tumor: From Mechanisms to Precision Immunotherapies

ABSTRACT Metabolic reprogramming is a core hallmark of malignant tumors. It facilitates the rapid growth of tumor cells and significantly modulates antitumour immune responses through metabolic interactions, affecting the success of immunotherapy. Despite recent breakthroughs in immunotherapy, most patients exhibit limited responses, and the underlying mechanisms are closely related to metabolic dysregulation within the tumor immune microenvironment. However, a comprehensive review of how to systematically leverage metabolic interventions to enhance immunotherapy efficacy is lacking. This review examines the competitive interactions between tumor and immune cells within essential metabolic pathways, including those involving glucose, amino acids, lipids, and nucleotides. This metabolic stress leads to the functional exhaustion of effector immune cells and activation of immunosuppressive cells, thereby promoting immune escape. Based on these mechanisms, we further summarize therapeutic strategies that target key metabolic enzymes to reshape the immune microenvironment and discuss their integration with strategies and clinical advances such as immune checkpoint blockade or CAR‐T cell therapy. This review systematically integrates the core mechanisms and cutting‐edge strategies at the intersection of metabolism and immunity, provides a theoretical framework and methodological reference for basic research and clinical translation in this area, and offers a theoretical basis and translational perspective for the development of synergistic metabolic–immunological therapeutic strategies.