Formate, a microbial byproduct boosted by exercise, plays a pivotal role in strengthening immune responses against tumors.
In a new study, researchers have uncovered how exercise might help the immune system fight cancer: by changing the gut microbiome in a way that boosts production of a compound called formate. This microbial byproduct, the study shows, plays a key role in helping immune cells slow tumor growth—at least in mice.
The study, published in Cell, has revealed a striking biological chain reaction in mice: exercise alters the gut microbiome, boosting production of formate, which in turn supercharges the body’s immune defenses against tumors. The discovery may help explain why exercise enhances the effectiveness of immunotherapy.
“We already knew that exercise increases the effectiveness of cancer immunotherapies,” said Marlies Meisel, Ph.D., senior author of the study and assistant professor of immunology at the University of Pittsburgh. “This study connects those dots by showing how exercise-induced changes in the gut microbiome boost the immune system and enhance immunotherapy efficiency via formate.”
A Chain Reaction from Treadmill to Tumor
The researchers began by asking a simple question: why does exercise help certain cancer treatments succeed? Immunotherapy drugs called immune checkpoint inhibitors (ICIs) unshackle the immune system to attack cancer cells. However, ICIs work for some people but not others. Exercise has been shown to improve their odds, but the mechanism was a mystery.
To explore this, lead author Catherine Phelps and colleagues trained mice to run on treadmills daily for four weeks. These mice, when later implanted with melanoma tumors, showed slower tumor growth and improved survival compared to their sedentary counterparts.