T cells demand massive energy to combat cancer; however, the metabolic regulators controlling antitumor T cell immunity have just begun to be unveiled. When studying nutrient usage of tumor-infiltrating immune cells in mice, we detected a sharp increase of the expression of a CrT (Slc6a8) gene, which encodes a surface transporter controlling the uptake of creatine into a cell. Using CrT knockout mice, we showed that creatine uptake deficiency severely impaired antitumor T cell immunity. Supplementing creatine to WT mice significantly suppressed tumor growth in multiple mouse tumor models, and the combination of creatine supplementation with a PD-1/PD-L1 blockade treatment showed synergistic tumor suppression efficacy. We further demonstrated that creatine acts as a “molecular battery” conserving bioenergy to power T cell activities. Therefore, our results have identified creatine as an important metabolic regulator controlling antitumor T cell immunity, underscoring the potential of creatine supplementation to improve T cell–based cancer immunotherapies.

T细胞需要大量能量来对抗癌症。然而，控制抗肿瘤T细胞免疫的代谢调节剂才刚刚被揭开面纱。在研究小鼠肿瘤浸润免疫细胞的营养成分使用情况时，我们检测到CrT（Slc6a8）基因的表达急剧增加，该基因编码控制肌酸向细胞摄取的表面转运蛋白。使用CrT剔除小鼠，我们发现肌酸摄取不足严重损害了抗肿瘤T细胞免疫力。在多种小鼠肿瘤模型中，向WT小鼠补充肌酸可显着抑制肿瘤生长，并且补充肌酸与PD-1 / PD-L1阻断治疗相结合可显示出协同的肿瘤抑制功效。我们进一步证明了肌酸起着“分子电池”的作用，可以保存生物能量来驱动T细胞的活动。因此，我们的结果表明肌酸是控制抗肿瘤T细胞免疫力的重要代谢调节剂，强调了补充肌酸改善基于T细胞的癌症免疫疗法的潜力。