Recently, researchers from the UPMC Hillman Cancer Center and the National Cancer Institute (NCI) have shown that changing the gut microbiome can improve immunotherapy for patients with advanced melanoma. The results of this phase 2 clinical trial were published online in the journal of Science.
In this study, a team of researchers from UPMC Hillman performed fecal microbiota transplantation (FMT) and anti-PD-1 immunotherapy on melanoma patients whose all available therapies (including anti-PD-1) failed, and then followed up the clinical and immunological results. NCI collaborators analyzed the microbiome samples of these patients to understand why FMT seems to enhance their response to immunotherapy.
The lead author of the study, a medical oncologist, member of the UPMC Hillman Cancer Immunology and Immunotherapy Program (CIIP), and assistant professor of medicine at the University of Pittsburgh, Dr. Diwakar Davar, said: “FMT is just a means to an end.” . “We know that the composition of the gut microbiome can change the likelihood of responding to immunotherapy. But what are`good` bacteria? There are approximately 100 trillion bacterial genes in the gut bacteria, and the number of bacterial genes in the personal microbiome It is more than 200 times of all human genes.
Fecal transplantation provides a way to capture a large number of candidate microorganisms, which can test trillions of microorganisms at a time to see if having “good” bacteria can make more people susceptible to PD-1 inhibitors. This study is one of the first to test the idea in humans.
Davar and colleagues collected stool samples from patients who responded very well to anti-PD-1 immunotherapy, and sent the samples through colonoscopy to patients with advanced melanoma who had never responded to immunotherapy before for pathogen testing. Then provide patients with the anti-PD-1 drug pembrolizumab. Among the 15 patients with advanced melanoma who received FMT and anti-PD-1 combination therapy, 6 had tumor reduction or stable disease that lasted more than one year.
Dr. Hassane Zarour, a cancer immunologist and CIIP co-leader of the study, said: “The probability of a spontaneous response to the second anti-PD-1 immunotherapy is very low for patients treated in this trial. Therefore, any positive response should be attributed to stool transplantation.”
In this study, analysis of samples collected from FMT recipients revealed that immunological changes in the blood and tumor sites showed that the activation of immune cells in responders increased, while the immunosuppression of non-responders increased. Artificial intelligence links these changes to the gut microbiome, which is most likely caused by FMT.
Davar and Zarour hope to conduct larger trials in patients with melanoma and evaluate whether FMT may be effective in treating other cancers. Ultimately, their goal is to replace FMT with a mixture containing the most beneficial microorganisms to enhance the effect of immunotherapy.
