Creatine shows early promise in boosting cancer immune response

Creatine, a common fitness supplement, may help immune cells mount a stronger response against cancer, according to researchers at UCLA Health Sciences. The finding could point to ways to improve cancer immunotherapy, though the work remains preclinical and has not shown that creatine helps cancer patients.

The study, published in , focused on dendritic cells, immune cells that identify tumor threats and help activate killer T cells. UCLA said the experiments in mice and human cells grown in the lab found that creatine increased dendritic cell activity and improved their ability to support anti-tumor immune responses.

Many cancer immunotherapies aim to activate killer T cells, but UCLA said only about 20% to 40% of patients see meaningful benefit from current approaches. The research team is studying whether strengthening dendritic cells, which help direct those T cells, could broaden the effects of immunotherapy.

Lili Yang, the study’s senior author and a UCLA professor of microbiology, immunology and molecular genetics, said the research suggests creatine may support more than the T cells that attack cancer. She said it may also energize the immune-cell network that helps guide them.

What the researchers found

UCLA said the team first looked at metabolic gene activity in dendritic cells that had moved into tumors in mice. They found that a gene tied to the creatine transporter, which brings creatine into cells, was more active in tumor-infiltrating dendritic cells than in dendritic cells from healthy tissue.

Researchers then created dendritic cells that lacked that transporter. According to UCLA, those cells survived less well, showed lower activity and were worse at priming T cells to recognize and attack tumors.

In lab tests, T cells grown with creatine-deficient dendritic cells multiplied less and produced fewer signaling molecules associated with an anti-cancer response, UCLA reported. The findings build on earlier work from Yang’s laboratory that found creatine could also strengthen cancer-fighting T cells.

Mouse tests and human cell experiments

The team also tested whether raising creatine levels would have the opposite effect. UCLA said daily creatine injections in mouse models of melanoma slowed tumor growth and increased the number and activity of dendritic cells inside tumors.

Those dendritic cells also produced more chemical signals that help draw other immune cells into the tumor area, according to the university. Metabolomics analysis showed that creatine raised ATP levels inside dendritic cells; ATP is the main energy molecule used by cells.

UCLA said the increased energy stores appeared to help maintain inflammatory signaling pathways needed for dendritic cell activation. The researchers described creatine as acting like an energy reserve for the cells while they compete with fast-growing tumor cells for nutrients.

The scientists also studied human monocyte-derived dendritic cells, which are used in work on dendritic cell cancer vaccines. In those lab experiments, creatine improved dendritic cell activation and strengthened the cells’ ability to stimulate human T cells against a cancer-associated target, UCLA said.

James Elsten-Brown, a co-first author and graduate student in Yang’s lab, said the findings raise two possible uses: giving creatine alongside immunotherapy or using it during production of dendritic cell-based vaccines. Neither use has been proved in patients.

Clinical trials still needed

UCLA cautioned that the results come from mouse studies and lab-grown human cells, not from human cancer trials. The university said the experimental strategy has not been tested in people or approved by the Food and Drug Administration as safe and effective for cancer treatment.

Creatine monohydrate has been used for decades and is generally considered safe at recommended doses, according to UCLA, but the researchers said people receiving cancer care should speak with their physician before taking any supplement.

UCLA said the next step is prospective clinical trials to test whether creatine supplementation can improve outcomes for patients receiving cancer immunotherapy. The research was funded by UCLA and cancer research grants, and the potential therapeutic strategy is the subject of a patent application filed by the UCLA Technology Development Group on behalf of the Regents of the University of California.

This story draws on original reporting from ScienceDaily.