UT Southwestern (UTSW) researchers have reported a discovery that healthy bacteria moving out of the gut can help to combat cancerous tumors in other parts of the body.
Intestinal Flora
The new research helps to make clear how the use of antibiotics can impact the success of cancer immunotherapy. This knowledge could help to develop better cancer treatments or improve the efficacy of existing ones.
Findings from the study, whose first author was graduate student Yongbin Choi, were published in the journal Science Immunology.
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Gut bacteria and therapy success
Research shows that, with immune checkpoint therapy (ICT), gut microbes travel from the intestines to the nymph nodes. They trigger immune cells – specifically, T cells and dendritic cells – when they get to their destinations to make that therapy effective. Without the movement of helpful bacteria to the lymph nodes, ICT lacks potency.
Scientists had observed a relationship between the makeup of the microbes present in the digestive tract and the efficacy of cancer immunotherapies, such as pembrolizumab (Keytruda) and ipilimumab (Yervoy), in previous research. One of those studies was led by Andrew Y. Koh, M.D., who is also involved in the current work.
Pembrolizumab (Keytruda) and ipilimumab are examples of immune checkpoint inhibitors. These drugs block immune checkpoint proteins from binding.
In spite of the observed association between gut bacteria and cancer immunotherapy, researchers did not reach a consensus on the right microorganism balance to improve cancer therapy. Studies have hinted at diverse helpful bacteria.
“Scientists have been stumped as to how bacteria inside your gut can have an impact on cancer in your lungs, breasts, or skin,” explained Koh, a UTSW associate professor of pediatrics and microbiology. “Now we understand that mechanism much better and, in the future, hope to use this knowledge to better fight cancer.”
How gut microbes work
To make their findings, Koh and his fellow researchers made use of mice with melanoma tumors. They wanted to ascertain the effects of immune checkpoint inhibitors on how gut microbes move through the animals’ bodies.
These drugs, which enhance the ability of the immune system to attack tumors, were found to promote inflammation in the digestive tract. This brings about a remodeling of the gut’s lymph nodes, as per researchers.
The team found that these changes enable gut microbes to exit the intestines and go to nymph nodes near tumors or tumors themselves. This leads to the triggering of certain immune cells and the killing of tumor cells.
“Immune checkpoint inhibitors work by releasing the brakes on the immune system to target cancer,” Koh said. “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.”
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Going by the findings, a course of antibiotics can stand in the way of immune checkpoint inhibitors. Antibiotic use leads to the purge of most gut bacteria, thus impeding their ability to boost the immune system.
This study also sheds more light on why some previous studies suggested distinct beneficial bacteria. Koh explained that what’s most important is for beneficial bacteria to find their way to lymph nodes or tumors – it matters less what exact bacteria are involved.
The researchers are now working to develop bacterial-based therapies that would enhance immune checkpoint inhibitors’ effectiveness.
