Creatine Enhances Immune Cells to Boost Cancer Immunotherapy Potential

Creatine supplementation has been shown to enhance the function of immune cells involved in fighting cancer, according to a recent study conducted at UCLA. The research highlights creatine’s role in strengthening both killer T cells and dendritic cells, which are critical in initiating and directing immune responses against tumors.

Published in the journal iScience, the investigation involved experiments on mouse models and human cells. It builds on earlier findings by the same team that demonstrated creatine’s ability to boost killer T cell activity, which directly attacks cancer cells. The new results reveal that creatine also enhances dendritic cells, the immune cells responsible for detecting tumor antigens and activating killer T cells to respond.

How Creatine Supports Immune Cell Function

The researchers first examined metabolic gene activity in dendritic cells within tumors in mice. They discovered that these dendritic cells expressed significantly higher levels of the gene encoding the creatine transporter protein, which facilitates creatine uptake, compared to dendritic cells in healthy tissue.

To assess the importance of this, dendritic cells lacking the creatine transporter were engineered. These modified cells showed reduced survival, diminished activation, and impaired capacity to prime T cells for tumor attack. When cultured with T cells, the creatine-deficient dendritic cells led to lower T cell proliferation and decreased release of signaling molecules essential for an effective anti-cancer immune response.

Further experiments tested whether increasing creatine availability could improve dendritic cell performance. Daily creatine injections in melanoma mouse models slowed tumor progression and increased both the quantity and activity of dendritic cells within tumors. These cells also secreted more chemical signals that attracted additional immune cells to the tumor site.

Creatine’s Role in Enhancing Immunotherapy

Metabolomic analysis indicated that creatine supplementation raised ATP levels inside dendritic cells. ATP provides the energy required for cellular functions, and elevated ATP helped sustain inflammatory signaling pathways necessary for dendritic cell activation. The researchers likened creatine to a rechargeable battery that maintains dendritic cells’ energy supply even as they compete with rapidly growing tumor cells for nutrients.

In human cell studies, creatine treatment improved activation of monocyte-derived dendritic cells, which are commonly used in dendritic cell cancer vaccines. It also enhanced their ability to stimulate human T cells against cancer-related targets. These findings imply that incorporating creatine during dendritic cell vaccine production could increase vaccine effectiveness.

James Elsten-Brown, a co-first author and graduate student in the laboratory, stated, “Creatine could be used in two complementary ways: as a supplement to boost the immune response of patients undergoing immunotherapy, and as a tool to improve dendritic cell-based vaccines before administration.”

Study Limitations and Future Directions

The study suggests creatine may reinforce the body’s anti-cancer immune response at multiple stages, including the initial recognition of tumors by immune cells and the subsequent activation of killer T cells.

Co-first author Elliot Kang, a former undergraduate researcher, emphasized, “Supporting dendritic cells metabolically means supporting the entire anti-tumor immune response, not just the killer T cells at the end.”

The researchers caution that these findings derive from cell and animal models, not human clinical trials. Therefore, the study does not endorse any dietary or medical recommendations. Although creatine monohydrate has been used safely as a supplement for decades at recommended doses, patients receiving cancer treatment should consult their physicians before using any supplements.

Plans are underway to collaborate with physicians on clinical trials to evaluate whether creatine supplementation can improve outcomes for patients receiving immunotherapy.

The experimental methods described have not been tested in humans or approved by the Food and Drug Administration for safety and efficacy in human use.

The study, titled “Creatine uptake promotes dendritic cell activation and enhances antitumor immunity,” was authored by Elliot Kang, James Elsten-Brown, Yu-Chen Wang, Ashley Lam, Elise Sanchez, Renee Wen, Tiffany Wang, Jennifer Chiang, Quentin Scarborough, Yan-Ruide Li, Yichen Zhu, Jie Huang, Matthew Williams, Sarah Eckl, Bo Li, and Lili Yang, and published on March 21, 2026, in iScience (DOI: 10.1016/j.isci.2026.115436).

Funding was provided by a UCLA Broad Stem Cell Research Center Rose Hills Foundation Innovator Grant; the UCLA Health Jonsson Comprehensive Cancer Center and UCLA Broad Stem Cell Research Center Ablon Scholars Program; and a Magnolia Council Senior Investigator Grant Award along with a fellowship from the Tower Cancer Research Foundation.