Abstract: Metabolic reprogramming of the tumor microenvironment(TME)is a critical driver of malignant progression, immune evasion, and therapeutic resistance in cancer. Among the most prominent metabolic alterations, aerobic glycolysis, known as the Warburg effect, engages in bidirectional crosstalk with antitumor immunity. Even under normoxic conditions, tumor cells aberrantly activate glycolytic pathways and exploit multiple remodeling mechanisms-including glucose competition, lactate accumulation, extracellular acidification, and lactylation-to establish an immunosuppressive TME. This metabolic rewiring suppresses the activation, infiltration, and cytotoxic functions of effector immune cells, while simultaneously promoting the recruitment and functional maintenance of immunosuppressive populations such as regulatory T cells(Tregs), tumor-associated macrophages(TAMs), and myeloid-derived suppressor cells(MDSCs), thereby facilitating immune evasion and attenuating the efficacy of immunotherapies. Conversely, the activation, differentiation, and homeostatic maintenance of immune cells are strictly dependent on specific glycolytic programs, and the differential metabolic adaptability among immune cell subsets profoundly influences the immune equilibrium within the TME. Accumulating evidence indicates that tumor glycolytic pathways engage in positive feedback regulatory loops with classical immunosuppressive axes, including the programmed cell death protein 1/programmed death-ligand 1(PD-1/PD-L1)and the ectonucleoside triphosphate diphosphohydrolase 1/ecto-5'-nucleotidase(CD39/CD73)-adenosine pathways, which may represent a pivotal mechanism underlying the limited efficacy of immune checkpoint inhibitors. In recent years, targeted modulation of key glycolytic molecules, improvement of the metabolic-immune landscape of the TME, and combination with immunotherapy have emerged as important research directions in precision oncology. This review systematically summarizes the core molecular regulatory mechanisms of the Warburg effect, delineates the multiple pathways through which glycolytic reprogramming induces immunosuppression, characterizes the glycolytic metabolic adaptations of distinct immune cell subsets, and elucidates the interplay between glycolytic metabolism and immune signaling pathways. Furthermore, we review glycolytic-targeted intervention strategies and relevant clinical progress, analyze the major challenges hindering clinical translation of current research findings, and discuss future directions leveraging emerging technologies such as spatial multi-omics and cell metabolic engineering, with the aim of providing a theoretical foundation for the development and clinical application of metabolism-immunity combination therapeutic strategies.

Key words: Tumor microenvironment, Glycolytic reprogramming, Warburg effect, Lactylation, Tumor immunity, Immune evasion