Creatine uptake regulates CD8 T cell antitumor immunity

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.

Source: The Journal of Experimental Medicine - December 1, 2019 Category: Internal Medicine Authors: Di Biase, S., Ma, X., Wang, X., Yu, J., Wang, Y.-C., Smith, D. J., Zhou, Y., Li, Z., Kim, Y. J., Clarke, N., To, A., Yang, L. Tags: Tumor Immunology, Metabolism Articles Source Type: research