Creatine uptake regulates CD8 T cell antitumor immunity

Abstract

Di Biase et al. show for the first time that creatine acts as a “molecular battery” conserving bioenergy to power CD8 T cell activities; that creatine uptake is critical in supporting antitumor T cell immunity; and that creatine supplementation holds promise for improving cancer immunotherapy.

Pneumonia recovery reprograms the alveolar macrophage pool

“…The alveolar macrophages that remodeled after pneumococcal pneumonia displayed elevated creatine without a skewing toward "alternative" activation, but it is possible that creatine may influence chromatin accessibility and transcriptome changes in this setting as well. Increased Slc6a8 expression and elevated intracellular creatine also contribute to the efficacy of tumor-infiltrating CD8 + T cells, likely via energy metabolism (50). Together with our data, these observations suggest that enhancing creatine uptake may emerge as a broadly applicable means for immune cells to orient and augment their activities.…”

Creatine in Health and Disease

“…As performance-related studies assessed health and safety markers, evidence began to accumulate that creatine supplementation may also offer some health and/or therapeutic benefits as we age [ 4 , 12 , 14 , 67 , 69 , 70 , 71 , 131 ]. In this regard, creatine supplementation has been reported to help lower cholesterol, triglycerides and/or manage blood lipid levels [ 77 , 132 , 133 ]; reduce the accumulation of fat on the liver [ 133 , 134 ]; decrease homocysteine thereby reducing risk of heart disease [ 30 , 135 ]; serve as an antioxidant [ 30 , 136 , 137 , 138 , 139 ]; enhance glycemic control [ 1 , 11 , 140 , 141 , 142 , 143 ]; reduce the progress of some forms of cancer [ 8 , 17 , 18 , 135 , 144 , 145 , 146 , 147 ]; increase strength and muscle mass [ 2 , 9 , 13 , 67 , 70 , 71 , 93 , 99 , 101 , 148 , 149 , 150 , 151 , 152 ,…”

“…While these well-recognized creatine effects benefit the athlete, creatine may also serve as a potential clinical and therapeutic supplementary treatment to conventional medical interventions [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ]. In this regard, over recent years, researchers have been investigating the potential therapeutic role of creatine supplementation on health-related conditions such as diabetes [ 11 ], sarcopenia [ 4 , 6 , 12 , 13 ], osteoporosis [ 2 , 14 ], cancer [ 10 , 15 , 16 , 17 , 18 ], rehabilitation [ 4 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ], cognition [ 3 , 27 , 28 , 29 ], and cardiovascular health [ 5 , 6 , 8 , 30 , 31 , 32 ], among others. This work has increased interest in creatine use as a nutritional strategy to help maintain functional and mental capacity and, as we age, reduce risk to chronic disease, and/or serve as an adjunctive intervention to help manage disease and/or promote recovery.…”

Targeting monoamine oxidase A-regulated TAM polarization for cancer immunotherapy

“…The Phoenix-ECO-MIG, Phoenix-ECO-MIG-Maoa, and PG13-ESO-TCR stable virus producing cell lines were generated in this study. The MIG (MSCV-IRES-GFP) retroviral vector was reported previously 99,100,101 .…”

“…MIG retroviral vector was reported previously 99,100,101 . Codon-optimized Maoa cDNA (synthesized by IDT) was inserted into a MIG retroviral vector to generate the MIG-Maoa retroviral vector.…”