Glycolytic reprogramming in cancer: immune crosstalk, nutrient competition, and supportive care perspectives

Cancer-associated glycolytic reprogramming has long been recognized as a hallmark of malignant metabolism, yet its importance extends far beyond supporting tumor growth and biosynthesis. Increasing evidence indicates that enhanced glycolysis profoundly reshapes the tumor microenvironment by redistributing nutrients, increasing lactate accumulation, and creating acidic, immunosuppressive conditions. Through these changes, tumor glycolysis influences not only cancer cell survival but also the function of immune and stromal populations, thereby linking metabolic adaptation to immune escape and therapeutic resistance. In particular, excessive glucose consumption by tumor cells restricts nutrient availability for effector lymphocytes, whereas lactate and acidification impair T-cell fitness, promote suppressive myeloid phenotypes, and support fibroblast-mediated immunosuppressive niche formation. In parallel, glycolysis-associated signaling programs can directly regulate immune checkpoints such as PD-L1, further integrating tumor metabolism with immune evasion. These findings support a broader view of glycolysis as an organizer of tumor immune ecology rather than a purely tumor-intrinsic metabolic event. In this review, we discuss the molecular basis of glycolytic reprogramming, its role in immune crosstalk and nutrient competition, and its contribution to resistance against radiotherapy, chemotherapy, and immunotherapy. We further highlight emerging therapeutic opportunities, including direct glycolysis targeting, metabolism-directed nanomedicine, nutritional intervention, and metabolic engineering of immune cells. Together, these advances suggest that effective future strategies should combine tumor metabolic restriction with restoration of immune metabolic fitness.