Man in a hospital bed

Melanoma is the deadliest form of skin cancer, and it often doesn’t respond to typical treatments.

But researchers at UPMC Hillman Cancer Center and the National Cancer Institute (NCI) report a way to help patients’ responses.

According to a study published in Science, researchers show that changing the gut microbiome can help turn patients with advanced melanoma who aren’t responding to immunotherapy into patients who do respond.

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How Did the UPMC Study Work?

Immunotherapy is a common cancer treatment, but it has a failure rate of 40% for advanced melanoma.

One type of immunotherapy attempts to block PD-1, a protein found on your immune system’s T cells. PD-1 can keep T cells from killing cancer cells. Anti-PD-1 immunotherapy attempts to block PD-1 so T cells can kill cancer cells.

The UPMC Hillman phase II clinical trial targeted advanced melanoma patients who had no response to all available traditional and/or immunotherapies, including anti-PD-1.

In the study, UPMC Hillman researchers gave fecal microbiome transplants (FMT) and anti-PD-1 immunotherapy to the patients.

The fecal samples came from patients who had responded very well to anti-PD-1 immunotherapy. After testing the fecal samples for infectious pathogens, doctors transplanted them into the advanced melanoma patients through colonoscopy.

The researchers then tracked the patients’ clinical and immunological outcomes.

“FMT is just a means to an end,” says Diwakar Davar, MD, a medical oncologist and member of the Cancer Immunology and Immunotherapy Program (CIIP) at UPMC Hillman. Dr. Davar was the co-lead author of the study.

“We know the composition of the intestinal microbiome — gut bacteria — can change the likelihood of responding to immunotherapy,” Dr. Davar says. “But what are ‘good’ bacteria? There are about 100 trillion gut bacteria and 200 times more bacterial genes in an individual’s microbiome than in all of their cells put together.”

A fecal transplant can capture a large number of microbes and allow researchers to test trillions at once. They can see whether having the “good” bacteria on board can make more people sensitive to PD-1 inhibitors. This was one of the first studies to test the effect.

What Were the Results of UPMC’s Fecal Microbiome Transplant Study?

The advanced melanoma patients who received the fecal transplants had previously failed all available immunotherapies, including anti-PD-1.

After the patients received the transplants, doctors gave them the anti-PD-1 drug pembrolizumab.

This time, the therapy had success. Out of 15 advanced melanoma patients who received the combined treatment, six showed either tumor reduction or disease stabilization lasting more than a year.

“The likelihood that the patients treated in this trial would spontaneously respond to a second administration of anti-PD-1 immunotherapy is very low,” says study co-senior author Hassane Zarour, MD, a cancer immunologist and co-leader of the CIIP at UPMC Hillman. “So any positive response should be attributable to the administration of fecal transplant.”

NCI researchers analyzed microbiome samples from these patients to understand why FMT seemed to boost their response to immunotherapy.

Analysis of samples taken from FMT recipients in this study revealed immunologic changes in the blood and at tumor sites. This suggested increased immune cell activation in responders and increased immunosuppression in nonresponders.

Artificial intelligence linked these changes to the gut microbiome, likely caused by FMT.

Dr. Davar and Dr. Zarour hope to run a larger trial with melanoma patients. They also hope to evaluate whether FMT could help treat other cancers.

Ultimately, the goal is to replace FMT with pills containing a cocktail of the most beneficial microbes for boosting immunotherapy. That possibility is still years away.

“Even if much work remains to be done, our study raises hope for microbiome-based therapies of cancers,” Dr. Zarour says.

Why Choose UPMC Hillman Cancer Center?

UPMC Hillman Cancer Center is the only comprehensive cancer center in western Pennsylvania, as designated by the National Cancer Institute.

Our multidisplinary team of experts provides world-class care to each patient, from diagnosis to treatment and beyond. We provide cutting-edge treatment options, and our researchers are finding new ways to prevent, detect, and treat cancer.

For more about UPMC Hillman, call 412-647-2811 or visit us online.

Sources

National Cancer Institute, PD-1. Link

About UPMC Hillman Cancer Center

UPMC Hillman Cancer Center provides world-class cancer care, from diagnosis to treatment, to help you in your cancer battle. We are the only comprehensive cancer center in our region, as designated by the National Cancer Institute. We have more than 70 locations throughout Pennsylvania, Ohio, New York, and Maryland, with more than 200 oncologists. Our internationally renowned research team is striving to find new advances in prevention, detection, and treatment.