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Lactate is a compound that is produced primarily in the muscles via the breakdown of glucose during exercise. It can be “shuttled” from the muscles to various tissues, including the heart, and brain, where it can be used as an energy source. Evidence from a recent study suggests that lactate rejuvenates immune cells that target cancer.
Specialized immune cells called CD8+ T cells are the primary drivers of anti-tumor immunity. During cancer progression, CD8+ T cells can experience “exhaustion,” a dysfunctional state caused by immune-related tolerance and immunosuppression in the environment surrounding the tumor.
Researchers injected either lactate or glucose into mice that had cancer. The lactate markedly reduced cancer growth, but the glucose had little effect. They determined that the anti-tumor response was mediated by the CD8+ T cells. Depleting the CD8+ T cells negated lactate’s effect, confirming that lactate promotes anti-tumor immunity through CD8+ T cells.
They also measured metabolites produced by CD8+ T cells (in culture) that had been treated with lactate. They found that the cells' uptake and subsequent metabolism of lactate increased. In addition, lactate inhibited the activity of histone deacetylases, and in turn, promoted the cells' stemness – the strictly controlled molecular processes that drive stem cell self-renewal and replication.
These findings suggest that lactate rejuvenates the immune cell populations that target cancer, providing a possible mechanism by which exercise – which increases lactate production – reduces the risk of cancer. Learn more about lactate and the lactate shuttle in this episode featuring Dr. George Brooks.
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