Could Gut Bacteria Help Unlock Immunotherapy's Potential?

In a study published in Science Immunology, researchers at Washington University School of Medicine in St. Louis describe their discovery that a specific strain of gut bacteria, Ruminococcus gnavus, can enhance the effects of cancer immunotherapy in mice. This finding suggests a promising new strategy to improve the effectiveness of immunotherapy and benefit more cancer patients.

"The microbiome plays an important role in mobilizing the body's immune system to attack cancer cells," explained the study's senior author, Marco Colonna. "Our findings shine a light on one bacterial species in the intestine that helps an immunotherapy drug eliminate tumors in mice. Identifying such microbial partners is an important step in developing probiotics to help improve the effectiveness of immunotherapy drugs and benefit more cancer patients."

Cancer immunotherapy harnesses the body's immune cells to target and destroy tumors, but some tumors can suppress the attacking immune cells, reducing the treatment's efficacy. In a surprising observation, the researchers found that mice lacking a protein called TREM2 experienced the same beneficial response to immunotherapy when housed with mice that had the protein, suggesting that the effects were due to the exchange of gut bacteria.

Further investigation revealed an expansion of Ruminococcus gnavus in the gut microbiota of mice that responded well to immunotherapy, compared to a lack of such microbes in non-responders. Notably, R. gnavus has also been found in the gut microbiota of cancer patients who respond well to immunotherapy.

When the researchers introduced R. gnavus to the mice and treated their tumors with a checkpoint inhibitor, the tumors shrank, even when TREM2 was present to dampen the treatment's effect.

Jeffrey I. Gordon, co-author of the study, noted that evidence is mounting that the microbiota boosts immunotherapy. "Identifying relevant species, such as R. gnavus, could lead to a next-generation probiotic that could synergize with immunotherapy to improve cancer care," he explained.

The researchers aim to understand how R. gnavus assists in tumor rejection, which may reveal new ways to help cancer patients. For example, if the microbe produces an immune-activating metabolite, that knowledge could lead to the use of metabolites as immunotherapy enhancers.