March 15, 2018
Could the microbiome change the future of cancer treatment?
BY Gillian Kruse
We practice hand hygiene to help keep ourselves from getting sick from the bacteria all around us. But each of us already has a huge population of bacteria on and inside us: our microbiome.
It’s impossible to count every cell and microbe, but it’s estimated that each person has at least as many bacteria in their body as their own cells, if not more.
If we have trillions of bacteria all around us, then why aren’t we constantly sick? MD Anderson scientists are finding that the microbiome, especially our gut microbiome, plays an important role in keeping our bodies healthy.
Improving cancer treatment for melanoma patients
Immunotherapy drugs have been a great success for some cancer patients, training their own immune systems to attack the cancer cells. These treatments don’t always help, though, and as part of our Melanoma Moon Shot™, doctors have been searching for answers as to why some patients have great responses to immunotherapies and others don’t respond at all.
Along with her team, Jennifer Wargo, M.D., co-leader of the Melanoma Moon Shot, is studying how the makeup of the gut microbiomes in her melanoma patients affect their response to anti-PD-1 immune checkpoint blockade therapies.
Preliminary results show that the patients who responded best to the anti-PD-1 treatments also had the most diversity of microbes in their guts, as well as types of bacteria that are different than those who didn’t respond to the treatment.
“Now that we’ve documented these differences, we’re hoping to find ways to help those patients who don’t have good responses on their own,” Wargo says. “The gut microbiome shapes much of how our immune system functions, and anything that changes the microbiome can change your response to treatment as well.”
The next step for Wargo and her colleagues, in collaboration with the Parker Institute for Cancer Immunotherapy and Seres Therapeutics, is to develop a clinical trial to test the safety of modulating the microbiome in patients receiving checkpoint blockade.
Reducing stem cell transplant side effects
Physicians who work with stem cell transplant patients were the first to connect the microbiome to overall health. Studying transplants in germ-free mouse models, they saw that if you give a germ-free mouse a transplant, it doesn’t experience graft-versus-host disease (GVHD), a serious and potentially lethal side effect from the transplant process. So they knew that the microbiome played a role in the body’s response to the transplant – and the new immune system’s response to the patient’s healthy cells.
It’s impractical to eliminate patients’ microbiomes and keep them in completely germ-free settings during the transplant process, especially when some patients never contract GVHD at all. But what could be done for the patients who do experience GVHD?
In analyzing the charts of previous transplant patients, Robert Jenq, M.D., and his colleagues noticed a pattern in those without acute GVHD. They were given narrower spectrum antibiotics than standard treatment, often due to a penicillin allergy.
Seeing that there could be a connection between antibiotic use and GVHD, they collected stool samples right before transplant, as well as upon the development of GVHD (if applicable) to learn what bacteria were in each patient’s microbiome. They found that patients with lower microbial diversity and more injury to their original microbiome were at a higher risk for GVHD.
“Now that we’ve seen these results and other groups have replicated them, we want to see if it’s possible to use intestinal bacteria like a biomarker to predict who’s going to do well and who is at high risk for GVHD,” Jenq says. “If we can, we could intervene and potentially open up a whole new area of therapy.”
Patients who undergo harsh chemotherapies often end up immunosuppressed and susceptible to infection. Many of these infections require them to be admitted for treatment, which in turn puts the patients into an environment where they could acquire more infections.
Using what we know about the microbiomes in healthy people to find ways to prevent infection in our sick patients is the goal of Samuel Shelburne, M.D., Ph.D. He works with leukemia patients, our most immunocompromised population, to determine why some patients develop serious infections and others don’t.
Since the loss of healthy microbes can make a person more susceptible to infection, Shelburne and his team are working to learn about what they can do to help patients maintain healthy microbiomes.
“Many infections arise from bacteria people already have in their system and environment,” he says. “Keeping the microbiome stable could be a way to prevent these infections and keep our patients out of the hospital.”
Our researchers are looking at the use of various antibiotics as well as the possibility of introducing good bacteria to help combat the bad. Eventually, they want to determine who’s a low infection risk and could shift to outpatient chemotherapy treatments, making the patients less likely to acquire an infection in the hospital.
“This is a completely new branch of science, and we’re learning more and more every day,” he says. “Ten years ago we didn’t have the screening techniques to do this, and as we continue to refine how we study the microbiome, we’ll be able to find real results to make a big difference in how we treat cancer.
A longer version of this story originally appeared in Messenger, MD Anderson’s quarterly publication for employees, volunteers, retirees and their families.
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TopicsMelanoma Skin Cancer Clinical Trials Immunotherapy Side Effects Leukemia Moon Shots Program Treatment Stem Cell Transplantation Cellular Therapy Research Chemotherapy
Anything that changes the microbiome can change your response to treatment as well.
Jennifer Wargo, M.D.