Could the microbiome change the future of cancer treatment?

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.”

Stopping infections

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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