First-of-a-kind fecal transplants assist in treatment of unresponsive melanomas
As part of our ever-expanding toolbox in the fight against cancer, scientists are investigating how altering the gut microbiome through fecal transplants can help swing things in our favor. Where this may prove extremely valuable is in patients who have not responded to other available treatments, and in a promising new study, scientists have demonstrated how this technique can deliver positive outcomes in advanced melanoma sufferers who fall into exactly that category.
Recent research has started uncover the incredibly diverse ways that our gut bacteria can impact our health, including how it can influence the efficacy of certain drugs. One example of this is are cancer drugs known as PD-1 checkpoint inhibitors, which improve the immune system’s ability to fight cancer, though only work in around a quarter of patients.
In 2017, we looked at research that examined the role a patient’s gut bacteria might play in this, and potentially determine whether or not they responded to the treatment. The scientists found that patients who had recently taken antibiotics were substantially lacking in certain gut bacteria species, and had far less success with the PD-1 treatment as a result.
Those scientists then carried out experiments where fecal matter was taken from the humans that had responded to PD-1 treatment and transplanted it into mice. These mice subsequently responded positively to the drug. Another group of mice were given fecal transplants from the group of humans who had taken the antibiotics, and didn’t respond as well.
Now, scientists at the University of Pittsburgh have conducted what they say is the first clinical trial to test out this idea in humans. Fecal samples were collected from patients that had responded “extraordinarily well” to PD-1 treatment and administered to advanced melanoma patients that had had never responded to any immunotherapy in the past.
Out of the 15 patients to receive the transplants, six of them showed either a tumor reduction or disease stabilization that lasted more than a year. The team’s analysis of the transplant recipients showed activity in line with an improved response to PD-1 treatment, such as increased activation of T cells and a decrease in cells that suppress the immune system. The team was able to link this to changes in the gut microbiome.
"The likelihood that the patients treated in this trial would spontaneously respond to a second administration of anti-PD-1 immunotherapy is very low," said study co-senior author Hassane Zarour, M.D. "So, any positive response should be attributable to the administration of fecal transplant."
The scientists hope to build on these promising results by conducting larger trials with more melanoma patients, and explore how the technique might be used to tackle other cancers. Rather than rely on fecal matter transplants, the end game here is to develop drugs that contain the necessary microbes to alter the gut microbiome in just the right ways.
The research was published in the journal Science.
Source: University of Pittsburgh via EurekAlert