From sports to oncology
A study conducted on mice by scientists from the University of California at Los Angeles showed that taking creatine helps to maintain the antitumor activity of CD8 T-lymphocytes (T-killers) for a long time. The researchers also found that creatine increases the effectiveness of existing immunotherapy interventions.
The results were obtained by studying the metabolic needs of lymphocytes infiltrating the tumor, which migrate into it to fight cancer cells. The group found that T-killers isolated from tumors have a large number of creatine carrier proteins on their surface that control its absorption by cells.
The researchers suggested that these tumor-fighting T lymphocytes increased their ability to take creatine for a good reason, so they conducted a series of experiments and determined what happens when they can't get it.
Genetically modified mouse models were created, in whose T-killers there was a deficiency of the CrT gene (Slc6a8) encoding the production of creatine transporter molecules. The researchers found that mice whose T-killers could not take creatine were less active in fighting tumors.
The group then tried to test their hypothesis from the opposite side by giving unmodified mice a daily dose of creatine comparable to the safe dose recommended for athletes and bodybuilders. The surge in creatine, which was injected into some mice and given to others as an oral supplement, made both groups better equipped to suppress the growth of skin cancer and colon cancer.
Taken together, these results show that T-killers really need creatine to fight cancer. Without it, they cannot do their job effectively.
Creatine occurs naturally in humans and other vertebrates, it is produced in the liver and kidneys. Its natural sources are meat and fish. In addition to this, creatine supplements are widely distributed among athletes and bodybuilders seeking to gain muscle mass and improve performance. The popularity of creatine supplements is due to the fact that cells with high energy needs (muscle, nerve) use creatine to accumulate additional energy when they need it most.
This discovery adds T-killers to the list of creatine-dependent cells using two different sources of energy. The first source is a metabolic process that converts glucose, amino acids and lipids into energy molecules of ATP. The secondary energy source is creatine, which absorbs excess energy (in this case, ATP) and stores it for release in case of emergency, so that the cell elements function until the nutrients arrive.
This "hybrid" creatine-based energy system allows T-killers to maximize the use of available energy in an environment where they have to compete with fast-growing tumor cells for nutrients.
The group combined creatine intake with PD-1/PD-L1 blockade therapy, a form of cancer immunotherapy that prevents T–cell depletion and is approved for the treatment of a wide range of oncological diseases, including melanoma, lymphoma, colon cancer, lung cancer, liver cancer, kidney cancer and cervical cancer. They found that creatine supplementation and anti-PD-1 blockade work synergistically, shifting the metabolic balance in favor of T-killers, allowing them to avoid exhaustion and effectively fight cancer for a long period.
It was found that the T-killers of four out of five mice treated with combination therapy completely eliminated colon cancer. The tumor did not appear for more than three months. In addition, repeated administration of tumor cells to these mice did not lead to a recurrence of the tumor for another six months.
As a next step, the group plans to repeat the experiments using mouse models of human tumors and human immune cells. If it is possible to reproduce the effects in human cells, work will be carried out to determine the correct dose, time and method of administration in order to test a creatine supplement to improve existing immunotherapy procedures in humans. Since the strategy has proven effective in a mouse model of melanoma and colon cancer, the researchers hope that the results can be applied to several types of cancer in humans.
Since creatine supplements have been widely used by bodybuilders and athletes over the past three decades, accumulated evidence indicates their safety when taken in appropriate doses. However, researchers recommend consulting a doctor before including creatine in the diet, since the supplement may carry the risk of drug interactions and other harmful side effects. There is a concern that prolonged use of creatine in high doses can lead to disruption of the liver, kidneys and heart.
Article by S. Di Biase et al. Creatine uptake regulates CD8 T cell antitumor immunity published in the Journal of Experimental Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert: Creatine powers T cells' fight against cancer.