Creatine uptake regulates CD8 T cell antitumor immunity

S Di Biase, X Ma, X Wang, J Yu, YC Wang… - Journal of Experimental …, 2019 - rupress.org
S Di Biase, X Ma, X Wang, J Yu, YC Wang, DJ Smith, Y Zhou, Z Li, YJ Kim, N Clarke, A To
Journal of Experimental Medicine, 2019rupress.org
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 …
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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