A team at UCLA has found that creatine, the widely used athletic supplement, does something nobody expected: it energises the immune cells that detect cancer and coordinate the body's attack against it. The study, published in iScience, shows that creatine powers not only the killer T cells that destroy tumours but also the dendritic cells that train and direct those T cells in the first place.
The senior author, Professor Lili Yang of UCLA's Department of Microbiology, Immunology and Molecular Genetics, describes the finding as a shift in how researchers think about supporting the immune response during cancer treatment. Most approved immunotherapies target killer T cells directly, yet only 20 to 40 percent of patients respond to them. The UCLA team's work suggests part of the problem may be upstream: if the dendritic cells that activate T cells are running low on energy, even the best T cell therapies will underperform.
The researchers discovered that the gene encoding the creatine transporter was markedly elevated in dendritic cells inside tumours compared with healthy tissue. When they engineered dendritic cells to lack that transporter entirely, the cells showed impaired survival, weaker activation, and a reduced ability to prime T cells. The reverse experiment produced more striking results. Daily creatine injections in mouse models of melanoma significantly slowed tumour growth, boosted both the number and activation of tumour-infiltrating dendritic cells, and increased the chemical signals that recruit additional immune cells to the site.
Metabolomic analysis revealed the mechanism: creatine raised intracellular ATP levels in dendritic cells, sustaining the inflammatory signalling pathways required for activation. In effect, creatine acts like a battery, helping dendritic cells maintain stable energy levels even when competing with fast-growing tumour cells for nutrients. The team also demonstrated that creatine enhanced the activation of human monocyte-derived dendritic cells, the type used in dendritic cell cancer vaccines, suggesting a practical path to improving existing vaccine manufacturing processes.
The researchers are careful to note that the work was done in cells and mice, not patients. No clinical recommendations should be drawn from it yet. But the findings are strong enough that the team plans to pursue prospective clinical trials testing whether creatine supplementation improves outcomes in patients receiving immunotherapy.