LOS ANGELES — A study from the University of California, Los Angeles suggests creatine may strengthen the immune system's fight against cancer. The study found that creatine boosts the activity of dendritic cells, specialized immune cells that detect tumors and activate killer T cells.

The findings were based on experiments in mice and human cells, and the study was published in the journal iScience. The results have not yet been tested in human patients. Approximately 20% to 40% of patients experience meaningful benefits from current cancer immunotherapies designed to activate killer T cells.

"Immunotherapy has shown remarkable promise, but it only works for a subset of patients," said Lili Yang, the study's senior author and a professor of microbiology, immunology and molecular genetics at UCLA. "What this study shows is that creatine doesn't just help the T cells fighting cancer -- it also energizes the entire infrastructure supports and guides them."

Researchers found that the gene responsible for producing the creatine transporter was more active in tumor-infiltrating dendritic cells in mice than in dendritic cells in healthy tissue. Engineered dendritic cells lacking the creatine transporter survived less effectively, became less active, and were less capable of preparing T cells to recognize and attack tumors in laboratory experiments.

Daily creatine injections in mouse models of melanoma slowed tumor growth and increased the number and activity of dendritic cells that had entered tumors. Treated dendritic cells released higher levels of chemical signals that attracted additional immune cells into the tumor environment. Metabolomics analyses indicated that creatine supplementation increased intracellular ATP levels in dendritic cells.

In laboratory experiments, creatine enhanced the activation of human monocyte-derived dendritic cells and improved their ability to stimulate human T cells against a cancer-associated target. "The potential we see here is that creatine could be used in two complementary ways: as a supplement to enhance the immune response of patients already receiving immunotherapy, and as a tool to improve the quality of dendritic cell-based vaccines before they're administered," said James Elsten-Brown, a co-first author and graduate student in Yang's lab.

"Understanding how to metabolically support dendritic cells is about supporting the entire anti-tumor response, not just the killer T cells at the end of it," said Elliot Kang, a co-first author of the study and former undergraduate student researcher in Yang's lab. The experimental approaches described in the study have not been approved by the Food and Drug Administration as safe and effective for use in people. A patent application regarding the potential therapeutic strategy was filed by the UCLA Technology Development Group on behalf of the Regents of the University of California.