Written by: Diego A. Bonilla, Richard B. Kreider, Kristen Drescher and Lili Yang
IN THIS ARTICLE
1. Introduction
2. Preclinical Research
3. Novel Findings
4. Where the Evidence Stands
5. The Take-Home Message
Introduction
One of the most interesting presentations at the CREATINE CONFERENCE 2025 came from Dr. Lili Yang at the University of California, Los Angeles. Her laboratory studies how creatine influences T cells, the immune system’s primary cancer-fighting cells.
When immune cells (whether they are T cells attacking a tumor or macrophages responding to an infection) become activated, they need to rapidly produce energy to divide, migrate, and release signaling molecules. The phosphocreatine/creatine kinase system is a well-known energy buffer in muscle and brain. The emerging question is whether it serves a similar role in immune cells.
Preclinical research
Using mouse models, her team found that tumor-infiltrating immune cells express high levels of the creatine transporter (SLC6A8), suggesting they have an increased need for creatine. When they deleted this transporter specifically in CD8+ T cells, those cells failed to control tumor growth. They showed impaired proliferation, reduced production of effector molecules like IFN-γ and granzyme B, and accelerated signs of exhaustion.
The core problem turned out to be energy. Without the ability to import creatine, T cells had lower intracellular ATP. Supplementing with ATP partially restored their function. In essence, the phosphocreatine/creatine kinase system acts as a metabolic “battery” (Figure 1) that helps T cells sustain the high energy demands of an effective anti-tumor response [1].
Importantly, when Professor Yang’s team gave creatine to tumor-bearing mice (either by injection or in the diet) tumor growth slowed, and CD8+ T cell activity inside the tumors increased. The effect was dependent on those T cells; it disappeared in mice lacking a functional immune system or depleted of CD8+ T cells.
Perhaps most promising, combining creatine with anti-PD-1 immunotherapy produced the strongest anti-tumor effects. This suggests that supporting T cell metabolism with creatine might enhance the effectiveness of existing immunotherapies.
Novel findings
While they often hold the frontline in an immune response, T cells aren’t the only immune cells involved in fighting the tumor, and they’re far from the only immune cells with high energy demands. A recent study from Dr. Yang’s lab indicated that dendritic cells, which are responsible for signaling for and activating the T cell response against cancer, also benefit from a creatine-derived energy buffer [2]. This dual benefit for two anti-tumor immune cell types is promising for creatine’s potential as a supplement for patients undergoing cancer therapy and suggests other key immune players may see a similar boon from the increased energy availability that creatine provides. And so, the research continues…
Where the Evidence Stands
It is important to be clear about what these findings do (and do not) mean.
First, research is in the preclinical stage, conducted in animal models. So, the information presented does not mean that creatine is a proven treatment for cancer. For cancer immunotherapy, the idea of combining creatine with checkpoint inhibitors is now a testable hypothesis.
As Professor Yang noted in her presentation, the phosphocreatine/creatine kinase system functions as a kind of battery, an energy reserve that cells can draw on when demand is high. For immune cells in a tumor, that reserve can mean the difference between an effective attack and exhaustion. For the gut microbiome, a metabolite of creatine may help tip the balance toward a more stable, less inflammatory community.
The Take-Home Message
The strongest evidence for creatine monohydrate remains in the domains of muscle strength, lean mass, and exercise performance, particularly when combined with resistance training. But the immune system is now part of the conversation. Ongoing research is exploring whether creatine can help T cells fight cancer more effectively. These are not yet clinical applications, but they are scientifically important directions that will shape the next generation of creatine research.
Creatine is not a stand-alone solution for cancer or autoimmune disease. But as a well-tolerated, extensively studied molecule with a strong safety record, it is increasingly being recognized as a tool for understanding (and possibly supporting) the complex interface between metabolism and immunity.
This blog is based on presentations by Prof. Lili Yang (University of California, Los Angeles) at the Creatine Conference 2025. The Creatine Conference was organized by the Creatine for Health Scientific Advisory Board (Alzchem Group AG – Creapure® and Creavitalis®), the Exercise and Sport Nutrition Laboratory (Texas A&M University), and the DBSS Research Division.
References
- Di Biase, S., et al. (2019). Creatine uptake regulates CD8 T cell antitumor immunity. J Exp Med, 216(12), 2869–2882.
- Kang, E., et al. (2026). Creatine uptake enhances dendritic cell activation and enhances antitumor immunity. iScience, 29(4), 115436.