Healthy gut bacteria can boost immunotherapy effectiveness

Researchers at UT Southwestern Medical Center (UTSW) have discovered how healthy bacteria can escape the intestine, travel to lymph nodes and cancerous tumours elsewhere in the body, and boost the effectiveness of certain immunotherapy drugs. Their findings, published in the journal Science Immunology, shed light on why antibiotics can weaken the effect of immunotherapies and could lead to new cancer treatments.

“Scientists have been stumped as to how bacteria inside your gut can have an impact on a cancer in your lungs, breasts or skin,” said Andrew Y Koh, an associate professor at UTSW. “Now we understand that mechanism much better and, in the future, hope to use this knowledge to better fight cancer.”

Previous studies, including one led by Koh, have shown an association between the composition of gut microbiomes — the microorganisms found inside the digestive tract — and the effectiveness of cancer treatments that target the immune system, including pembrolizumab (Keytruda) and ipilimumab (Yervoy). However, researchers have reached conflicting conclusions about the ideal balance of microorganisms to optimise therapy, with studies pointing to different beneficial bacteria.

Koh and colleagues used mice with melanoma tumours to probe how the drugs, called immune checkpoint inhibitors, affected the movement of gut microbes through the body. They found that immune checkpoint inhibitors, which boost the activity of the immune system against tumours, also cause inflammation in the digestive system that leads to remodelling of lymph nodes in the gut.

Due to these changes, bacteria can leave the intestines and travel to lymph nodes near the tumour and the tumour itself, the researchers found. Here, the microbes activate a set of immune cells that act to kill tumour cells.

“Immune checkpoint inhibitors work by releasing the brakes on the immune system to target cancer,” said Koh, who is also Director of the Cellular and ImmunoTherapeutics Program at UTSW and Children’s Health. “What we think is that these microorganisms and the immune cells they’re activating are essentially pressing on the accelerator of the immune system at the same time.”

The findings suggest that a course of antibiotics, which can eliminate most gut microbes, is detrimental to immune checkpoint inhibitors because the bacteria can no longer play this role of immune accelerant. It also helps explain why researchers have found many types of bacteria in patient microbiomes that seem to be beneficial for treatment.

“As long as a subset of beneficial bacteria can translocate from the gut to the lymph node or tumour, it may not matter exactly which bacteria it is,” Koh said. He and his team are now working toward the development of bacterial-based treatments to boost the efficacy of immune checkpoint inhibitors.

Image credit: iStock.com/ChrisGorgio