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In a new study, researchers from the University of Texas Southwestern Medical Center have discovered how healthy gut bacteria can escape the gut, enter cancerous tumors in lymph nodes and other parts of the body, and boost certain immune therapies.
In a new study, researchers from the University of Texas Southwestern Medical Center have discovered how healthy gut bacteria can escape the gut, enter cancerous tumors in lymph nodes and other parts of the body, and boost certain immune therapies. The effect of the drug. The discovery sheds light on why antibiotics can blunt the effectiveness of immunotherapy and could lead to new cancer treatments. The relevant research results were published in the journal Science Immunology in March 2023, with the title of the paper “Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity“.
Dr Andrew Y. Koh, associate professor of pediatrics and microbiology at UT Southwestern Medical Center and senior author of the paper, said, “Scientists have long wondered how the bacteria in your gut can affect cancer in your lungs, breasts or skin. We now know more about the mechanism and hope to use this knowledge to better fight cancer in the future.”
Previous research has shown the composition of the gut microbiome — the microbes found in the digestive tract. However, in existing studies, scientists have drawn conflicting conclusions on the question of the ideal microbial balance for optimal treatment, pointing to different beneficial bacteria.
Dr. Koh and colleagues used melanoma-bearing mice to explore how these immunotherapy drugs, called immune checkpoint inhibitors, affect the movement of gut microbes through the body. They found that immune checkpoint inhibitors boosted the immune system’s activity against tumors and also caused inflammation in the digestive system.
The authors found that as a result of these changes, gut bacteria can leave the gut and travel to lymph nodes near the tumor and to the tumor itself. There, the microbes activated a group of immune cells that acted to kill tumor cells.
“Immune checkpoint inhibitors target cancer by unsuppressing the immune system,” said Dr. Koh. “We think that these microbes and the immune cells they’re activating are essentially simultaneously hitting the accelerator on the immune system.”
These findings suggest that a course of antibiotics, which eliminates most gut microbes, is detrimental to immune checkpoint inhibitors because gut bacteria can no longer function as immune accelerators. It also helps explain why the scientists found many types of bacteria in the patient’s gut microbiomes that appeared to be therapeutically beneficial.
“As long as a subset of beneficial bacteria can migrate from the gut to lymph nodes or tumors, it probably doesn’t matter what kind of bacteria it is,” Dr. Koh said.
Dr. Koh’s team is now working to develop bacteria-based therapeutics to improve the efficacy of immune checkpoint inhibitors.
References:
Yongbin Choi et al. Immune checkpoint blockade induces gut microbiota translocation that augments extratestinal antitumor immunity . Science Immunology, 2023, doi:10.1126/sciimmunol.abo2003.
