J Exp Med. 2019 Dec 2;216(12):2869-2882. doi: 10.1084/jem.20182044. Epub 2019 Oct 18.
Creatine uptake regulates CD8 T cell antitumor immunity.
Di Biase S#1, Ma X#1, Wang X1, Yu J1, Wang YC1, Smith DJ1, Zhou Y1, Li Z1, Kim YJ1, Clarke N1, To A1, Yang L2,3,4,5.
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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.
© 2019 Di Biase et al.
PMID: 31628186 PMCID: PMC6888972 DOI: 10.1084/jem.20182044