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A study in mice suggests that doctors may be able to use gut bacteria to boost some immunotherapy treatments. Image design by MNT; Photography by NIH Image Gallery/Flickr & jose carlos cerdeno martinez/Getty Images.
  • Researchers investigated how gut bacteria influence the efficacy of immune checkpoint inhibitor (ICI) treatment in mice.
  • They found that ICIs allow certain gut bacteria to travel to tumor sites, where they activate the immune system to kill cancer cells.
  • Further study is needed to confirm whether these findings may apply to humans.

Immune checkpoint inhibitors (ICIs) are a kind of immunotherapy. They work by blocking specific proteins that moderate immune function, such as CTLA-4 or PD-1, thus “taking the breaks off” of the immune system so it can get rid of cancer cells.

However, up to half of patients with cancer do not respond to ICI treatments. A growing number of studies show that the gut microbiome may play a role in ICI treatment efficacy.

Research shows that mice that lack gut microbiota or that are treated with antibiotics respond less to ICI. Studies also suggest that replacing microbiota via fecal transplants may increase response from ICI.

It remains unclear which gut bacteria are most effective for increasing ICI response and how gut bacteria improve immune response.

Recently, researchers investigated how gut bacteria diversity influences ICI efficacy in a mouse model of melanoma.

They found that ICI treatment causes inflammation in the digestive system, allowing bacteria to leave the intestines and travel to lymph nodes near tumors, where they activate immune cells.

The study appears in Science Immunology.

Dr. Anton Bilchik, surgical oncologist and division chair of general surgery at Providence Saint John’s Health Center and chief of medicine and director of the Gastrointestinal and Hepatobiliary Program at Saint John’s Cancer Institute in Santa Monica, CA, not involved in the study, told Medical News Today:

“Since there is a plethora of research studying the impact of the gut microbiome on the immune system this provides a novel explanation as to how immunotherapy may work outside of the intestinal tract. Furthermore, it shows the deleterious effect that antibiotics may have in reducing the efficacy of immunotherapy by neutralizing bacteria within the gastrointestinal tract.”

For the study, the researchers administered ICI therapy to mice with and without melanoma tumors.

They found that ICI treatment increased inflammation in the digestive tract, which allowed certain bacteria to leave the gut and travel to lymph nodes near the tumor, as well as the tumor site. There, the microbes activated a set of immune cells that killed tumor cells.

The researchers also investigated how antibiotic exposure may affect ICI efficacy. To do so, they treated mice with antibiotics, then implanted them with melanoma tumors and treated them with ICI a week later.

They found that antibiotic exposure reduced gut microbiota movement to lymph nodes, and decreased immune cell levels.

Finally, they investigated whether administering different kinds of bacteria could reverse the effect of the antibiotics on ICI efficacy. They found that treatments with Escherichia coli and Enterococcus faecalis improved ICI efficacy.

MNT spoke with Dr. Andrew Koh, associate professor at the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern, senior author of the current study, about the study’s limitations.

A major limitation, noted Dr. Koh, is that they only used one preclinical cancer model, meaning that further tests are needed to know whether the findings may apply to other cancers, too.

“We believe that our findings could apply to other cancers too, but we have not generated data to support that supposition,” he said.

“There are published data that different human tumors harbor unique or distinct tumor microbiomes — and many of the predominant taxa are bacteria that typically reside in the gut. So our study may provide a mechanistic link or explanation as to how gut microbiota can travel from the gut and seed different types of human tumors,” added Dr. Koh.

Dr. Guilherme Rabinowits, a hematologist and medical oncologist at Miami Cancer Institute, part of Baptist Health South Florida, not involved in the study, also told MNT that “[i]t is very likely that the findings reported in this study apply to other cancer types, since the gut bacteria translocation is unlikely to be tumor-specific.”

“Unfortunately, without proper testing, it is impossible to say for sure,” he noted.

When asked about other limitations of the study, Dr. Bilchik added that it remains to be seen whether the findings translate to humans.

Dr. Lance Uradomo, an interventional gastroenterologist at City of Hope Orange County Lennar Foundation Cancer Center in Irvine, CA, not involved in the study, also told MNT that “the type of therapy applied for testing melanoma can be linked to adverse side effects, such as colitis.”

“Further study is needed before it is understood if microbiome therapy — and the correct application — is truly effective,” he added.

When asked about the study’s implications, Dr. Koh said that the findings beg the question of whether there may be more direct ways to deliver probiotic treatments to patients than via the intestines.

“Perhaps giving live oral precision probiotics — which are fraught with many logistical challenges, such as maintaining stable engraftment in the human gut, which can easily be derailed by exposure to antibiotics or changes in diet — is not the best way to administer gut microbiota-based therapies,” he noted.

To this end, he noted that his lab is currently developing microbiota-derived therapy that can be administered outside the gastrointestinal tract.

“We hope to submit this story by the end of this year. I have filed two patents and formed a startup company, Aumenta Biosciences, which is developing this technology. Aumenta was awarded its first NIH [National Institutes of Health] grant last year to develop this technology,” he commented.