Creatine, an organic acid commonly taken as a supplement by athletes and bodybuilders, overactivates an important type of immune cell that activates and primes the body’s key cancer-fighting cells, according to a new UCLA study.
The study, conducted using mouse models and human cells and published in iScience, builds directly on previous work from the same lab that showed creatine empowers killer T cells in their fight against tumors. Now, the researchers have discovered that creatine also provides energy to dendritic cells, specialized immune cells that capture tumor fragments and direct attacks by killer T cells.
Most approved cancer immunotherapies work by directly targeting killer T cells, but only about 20% to 40% of patients respond. Enhancing dendritic cells, which train and activate T cells, could provide a way to bring the benefits of immunotherapy to more patients.
Immunotherapy shows significant promise, but is only effective in some patients. This study shows that creatine not only helps T cells fight cancer, it also energizes the entire infrastructure that supports and guides them. This makes creatine a promising supplement to comprehensively support the immune response on which modern immunotherapy relies. ”
Lily Yang, lead author of the study, professor of microbiology, immunology, and molecular genetics, and member of UCLA’s Eli Edith Broad Center for Regenerative Medicine and Stem Cell Research
The researchers started by looking at which metabolic genes were most active in dendritic cells that had infiltrated tumors in mice. They found that the gene encoding the creatine transporter, a protein that draws creatine into cells, was significantly increased in dendritic cells inside tumors compared to healthy tissue.
To find out why, the researchers grew and studied dendritic cells that had been engineered to lack the creatine transporter completely. These cells showed impaired survival, reduced activation, and a weakened ability to stimulate T cells to mount a response against the tumor. When creatine-deficient dendritic cells were grown in parallel with T cells in a laboratory dish, those T cells divided less and produced fewer signaling molecules needed to fight cancer.
The research team then tested the opposite intervention. Instead of lowering creatine levels, the researchers increased creatine levels to see if this could enhance dendritic cell function. Daily injections of creatine in a mouse model of melanoma significantly slowed tumor growth and promoted both the amount and activation of tumor-infiltrating dendritic cells. Dendritic cells treated with creatine also produced high levels of chemical signals that drew additional immune cells into the tumor.
Using metabolomics analysis, the researchers found that creatine supplementation increases intracellular ATP levels in dendritic cells (ATP is the energy currency that cells use to power virtually every function) and maintains important inflammatory signaling pathways necessary for activation. Like a battery that stores and releases excess energy as needed, creatine helps dendritic cells maintain stable energy levels even when competing with rapidly growing tumor cells for nutrients.
The researchers also tested the effects of creatine on human dendritic cells. Creatine treatment enhanced the activation of human monocyte-derived dendritic cells, commonly used in dendritic cell cancer vaccines, and improved their ability to stimulate human T cells against cancer-related targets. The results of this study suggest that incorporating creatine during the production of dendritic cell vaccines may enhance their therapeutic efficacy.
“The potential we see here is that creatine can be used in two complementary ways: as a supplement to boost the immune response in patients already receiving immunotherapy, and as a tool to improve the quality of dendritic cell-based vaccines before administering them,” said co-first author James Elsten Brown, a graduate student in Yang’s lab.
These findings demonstrate that creatine is a potential tool to enhance the immune system’s anti-cancer response at multiple levels, including cells that detect threats and mount a response.
“Understanding how to support dendritic cells metabolically can help support the entire anti-tumor response, not just the killer T cells at the end of the anti-tumor response,” said Elliot Kang, co-first author of the study and a former undergraduate researcher in Yang’s lab.
The researchers stress that while the findings are scientifically promising, the study was done on cells and mice, not patients, and no dietary or medical recommendations should be drawn from it. Although creatine monohydrate has been widely used as a supplement for decades and is generally considered safe at recommended doses, people undergoing cancer treatment should consult their doctor before adding the supplement to their daily routine.
Next, the team hopes to work with doctors on a prospective clinical trial that could test whether creatine supplementation improves outcomes for patients receiving immunotherapy.
The experimental strategy described in this study has not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.
Funding for this research was provided by a UCLA Broad Stem Cell Research Center Rose Hills Foundation Innovator Grant. UCLA Health Johnson Comprehensive Cancer Center and UCLA Broad Stem Cell Research Center Abron Scholars Program. received a Magnolia Council Senior Investigator Grant Award and a fellowship from the Tower Cancer Research Foundation.
This newly identified potential therapeutic strategy is the subject of a patent application filed by the UCLA Technology Development Group on behalf of the University of California Board of Regents.
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Reference magazines:
Kang, E. Others. (2026). Creatine intake promotes dendritic cell activation and strengthens anti-tumor immunity. iscience. DOI: 10.1016/j.isci.2026.115436. https://www.cell.com/iscience/fulltext/S2589-0042(26)00811-4
