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Creatine uptake regulates CD8 T cell antitumor immunity.

  • Author(s): Di Biase, Stefano;
  • Ma, Xiaoya;
  • Wang, Xi;
  • Yu, Jiaji;
  • Wang, Yu-Chen;
  • Smith, Drake J;
  • Zhou, Yang;
  • Li, Zhe;
  • Kim, Yu Jeong;
  • Clarke, Nicole;
  • To, Angela;
  • Yang, Lili
  • et al.
Abstract

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.

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