Creatine uptake regulates CD8 T cell antitumor immunity

J Exp Med. 2019 Dec 2;216(12):2869-2882. doi: 10.1084/jem.20182044. Epub 2019 Oct 18.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Cell Line, Tumor
  • Creatine / administration & dosage
  • Creatine / deficiency
  • Creatine / metabolism*
  • Dietary Supplements
  • Energy Metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunomodulation*
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Models, Biological
  • Neoplasms / genetics
  • Neoplasms / immunology*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Tumor Microenvironment


  • Antigens, Neoplasm
  • Membrane Transport Proteins
  • creatine transporter
  • Creatine