The study investigates the hypothesis that overexpression of the glucose transporter GLUT1 in CAR-T cells can enhance their function and antitumor potency. By overexpressing GLUT1, the researchers observed increased glucose consumption, glycolysis, and oxidative phosphorylation, leading to reduced T cell exhaustion and increased Th17 differentiation. GLUT1 overexpression also induced metabolic reprogramming, including increased glutathione-mediated resistance to reactive oxygen species and inosine accumulation. When challenged with tumors, GLUT1 overexpressed CAR-T cells secreted more proinflammatory cytokines, showed enhanced cytotoxicity, and demonstrated superior tumor control and persistence in mouse models. These findings suggest that enhancing glucose availability through GLUT1 overexpression could improve the antitumor immune function of engineered T cell populations.The study investigates the hypothesis that overexpression of the glucose transporter GLUT1 in CAR-T cells can enhance their function and antitumor potency. By overexpressing GLUT1, the researchers observed increased glucose consumption, glycolysis, and oxidative phosphorylation, leading to reduced T cell exhaustion and increased Th17 differentiation. GLUT1 overexpression also induced metabolic reprogramming, including increased glutathione-mediated resistance to reactive oxygen species and inosine accumulation. When challenged with tumors, GLUT1 overexpressed CAR-T cells secreted more proinflammatory cytokines, showed enhanced cytotoxicity, and demonstrated superior tumor control and persistence in mouse models. These findings suggest that enhancing glucose availability through GLUT1 overexpression could improve the antitumor immune function of engineered T cell populations.