UT Southwestern Medical Center researchers have figured out how beneficial bacteria may leave the colon, find their way to lymph nodes and malignant tumors in other parts of the body, and increase the efficiency of certain immunotherapy medications.
The results, which were published in the journal Science Immunology, give insight into why antibiotics may reduce the effectiveness of immunotherapies and may lead to novel cancer treatments.
Andrew Y. Koh, M.D., Associate Professor of Pediatrics, Microbiology, and in the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern, explained that until now, scientists have been perplexed about how gut bacteria could affect cancer in other parts of the body such as the lungs, breasts, or skin. However, with the latest research, the mechanism behind this phenomenon is much clearer, and it is hoped that this knowledge can be utilized to enhance cancer treatments in the future.
Prior research, including one performed by Dr. Koh at UT Southwestern, has established a link between the makeup of gut microbiomes—the bacteria present within the digestive tract—and the efficiency of immune-targeting cancer medications such as pembrolizumab (Keytruda) and ipilimumab (Yervoy).
But researchers have come to different conclusions about the best mix of microorganisms for therapy, with different studies pointing to different good bacteria.
Dr. Koh and colleagues employed melanoma-tumor-bearing mice to investigate the effects of immune checkpoint inhibitors on the dissemination of gut bacteria.
They discovered that immune checkpoint inhibitors, which increase the immune system’s activity against malignancies, also promote digestive system inflammation, which results in the remodeling of lymph nodes in the stomach.
Researchers found that because of these changes, bacteria can leave the intestines and move to lymph nodes near the tumor and to the tumor itself. In this case, the microorganisms trigger a response from the immune system that results in the death of tumor cells.
According to Dr. Koh, who also serves as the Director of the Cellular and ImmunoTherapeutics Program at UTSW and Children’s Health, immune checkpoint inhibitors function by removing the brakes on the immune system to attack cancer. He added that their research suggests that the microorganisms and immune cells that the inhibitors stimulate simultaneously act as an accelerator for the immune system.
The results indicate that a course of antibiotics, which may kill the majority of gut bacteria, is harmful to immune checkpoint inhibitors because the bacteria can no longer operate as an immunological stimulant.
It also helps explain why scientists have found many types of bacteria in the microbiomes of patients that seem to help with treatment.
“As long as a subset of beneficial bacteria can translocate from the gut to the lymph node or tumor, it may not matter exactly which bacteria it is,” adds Dr. Koh.
Immune checkpoint inhibitors aren’t as effective as they could be, so Dr. Koh’s team is now working on treatments based on bacteria to make them more effective.
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