Changing Good Gut Bacteria May Help Melanoma Treatment

Advanced melanoma is hard to treat and can be fatal. But changing bacteria in your gut could be a game changer, dramatically boosting treatment effectiveness.

Millions of microorganisms, including bacteria, fungi, viruses, and their genes, live on and inside our bodies. All of these microbes make up what scientists call the microbiome. While it’s true some of these microorganisms can be harmful to your body, researchers studying the microbiome in detail over the past several decades have documented how beneficial microorganisms can have a significantly positive impact on health, according to the National Institute of Environmental Health Sciences.

Now, cancer researchers have found tweaking the gut microbiome may lead to an effective way to treat the most serious and potentially deadly form of skin cancer — melanoma.

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Other types of skin cancers are typically easier to treat with good results than melanoma. Melanoma, on the other hand, is more dangerous than the far more common basal and squamous cell skin cancers because melanoma is much more likely to spread to other parts of the body, if not caught and treated early, the American Cancer Society points out.

The key treatment for advanced melanoma is a type of immunotherapy called anti-PD-1. While anti-PD-1 drugs don’t kill melanoma cancer cells directly, they block a pathway that shields the malignant cells from a patient’s immune system. With the cancers cells no longer protected, the immune system is better able to fight the cancer, according to researchers at Johns Hopkins Kimmel Cancer Center, who are studying anti-PD1 immunotherapies.

While the treatment can be remarkably effective for some melanoma patients, it has a failure rate of 40 percent. But a study by UPMC Hillman Cancer Center and National Cancer Institute (NCI) scientists, published in the journal Science, offers hope there could be a way to help more patients with advanced melanoma respond to anti-PD-1 immunotherapy.

The researchers found changing the gut microbiome in people with advanced melanoma transformed a significant number of patients who never responded to treatment into patients who responded extraordinarily well to an anti-PD-1 drug.

How fecal microbiota transplants could help treat melanoma

The key to changing the balance of microorganisms in the patients’ microbiomes was the use of fecal microbiota transplants.

Simply put, a fecal microbiota transplant (FMT) involves collecting beneficial microorganisms in the feces of volunteers and introducing this material into the gastrointestinal system of someone whose gut microbiome lacks certain “good” microorganisms.

“FMT is just a means to an end,” said medical oncologist Diwakar Davar, MD, assistant professor of medicine at the University of Pittsburgh, and a member of the UPMC Hillman Cancer Center’s Cancer Immunology and Immunotherapy Program (CIIP). “We know the composition of the intestinal microbiome — gut bacteria — can change the likelihood of responding to immunotherapy. 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.”  

To find out of certain people had “good” bacteria that might have a positive impact on their cancer treatment, Davar and colleagues set out to see if melanoma patients who responded extraordinarily well to anti-PD-1 immunotherapy might have microbes in their gut microbiome that could specifically benefit melanoma patients in whom previous anti-PD-1 treatment did not work.

Testing the idea FMT could boost melanoma treatment

Their study, among the first to test the idea certain bacteria in the gut microbiome could help facilitate cancer immunotherapy in humans, involved taking fecal samples from melanoma patients who had successful anti-PD-1 immunotherapy. Then, after testing the patients’ feces to make sure the samples didn’t contain any infectious pathogens, the material was used for an FMT, given via colonoscopy, to advanced melanoma patients who had failed all available therapies, including anti-PD-1.

The goal was to see if having “good” bacteria added to their gut microbiome could make them sensitive to anti-PD-1 inhibitors. When the patients were given pembrolizumab, an anti-PD-1 drug, it worked for many — even when every other melanoma treatment had failed.

Out of 15 advanced melanoma patients who received the combined FMT and anti-PD-1 treatment, six experienced either shrinking of their tumors or disease stabilization lasting over a year, so far.

Scientists at the NCI analyzed microbiome samples from these patients to study why FMT appears to boost their response to immunotherapy. Their analyses showed patients with advanced melanoma who responded to therapy after receiving the FMT had immunologic changes in their blood and at tumor sites,  indications that immune cell activation had been boosted. In addition, by using artificial intelligence technology, the researchers were able to link these changes to the gut microbiome.

They concluded the beneficial changes resulting in the patients responding to therapy were most likely the result of the FMT. In fact, the odds the patients treated in this trial study who had failed anti-PD-1 immunotherapy initially would have spontaneously responded to a new round of anti-PD-1 immunotherapy  without the FMT were almost non-existent.

“So, any positive response should be attributable to the administration of fecal transplant,” concluded UPMC Hillman cancer immunologist Hassane Zarour, MD, a cancer immunologist and co-lead of the study with Davar.

Bottom line? Zeroing in on FMT to help beat melanoma and other cancers

Davar and Zarour plan to run a larger trial with melanoma patients. They also want to test whether FMT can be effective in treating other types of cancers. Eventually, they want to replace FMT with pills containing a cocktail of the most beneficial microbes for boosting immunotherapy

“Even if much work remains to be done, our study raises hope for microbiome-based therapies of cancers,” said Zarour, who holds the James W. and Frances G. McGlothlin Chair in Melanoma Immunotherapy Research at UPMC Hillman.

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