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Researchers at UPMC Hillman Cancer Center and the National Cancer Institute (NCI) demonstrate that changing the gut microbiome can transform patients with advanced melanoma who never responded to immunotherapy–which has a failure rate of 40% for this type of cancer–into patients who do.
The results of this proof-of-principle phase II clinical trial were published online today in Science. In this study, a team of researchers from UPMC Hillman administered fecal microbiota transplants (FMT) and anti-PD-1 immunotherapy to melanoma patients who had failed all available therapies, including anti-PD-1, and then tracked clinical and immunological outcomes. Collaborators at NCI analyzed microbiome samples from these patients to understand why FMT seems to boost their response to immunotherapy.
“FMT is just a means to an end,” said study co-lead author Diwakar Davar, M.D., a medical oncologist and member of the Cancer Immunology and Immunotherapy Program (CIIP) at UPMC Hillman and assistant professor of medicine at the University of Pittsburgh School of Medicine. “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.”
Fecal transplant offers a way to capture a wide array of candidate microbes, testing trillions at once, to see whether having the “good” bacteria on board could make more people sensitive to PD-1 inhibitors. This study is among the first to test that idea in humans.