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Fecal Microbiome Transplant Converts Melanoma Immunotherapy Non-Responders into Responders

Scientists at the NIH in collaboration with UPMC Hillman Cancer Center have shown how some patients with advanced melanoma that hasn’t responded to immune checkpoint inhibitor therapy, can be converted to immunotherapy responders by giving them a fecal microbiota transplant (FMT), taken from patients who had responded very well to immunotherapy. Results from the proof-of-principle Phase II study, reported in Science, suggest that introducing certain fecal microorganisms into a patient’s colon may help individuals respond to drugs that enhance the immune system’s ability to recognize and kill tumor cells.

“In recent years, immunotherapy drugs called PD-1 and PD-L1 inhibitors have benefited many patients with certain types of cancer, but we need new strategies to help patients whose cancers do not respond,” said study co-leader Giorgio Trinchieri, MD, chief of the Laboratory of Integrative Cancer Immunology in NCI’s Center for Cancer Research. “Our study is one of the first to demonstrate in patients that altering the composition of the gut microbiome can improve the response to immunotherapy. The data provide proof of concept that the gut microbiome can be a therapeutic target in cancer.”

Trinchieri and colleagues report on their trial results in a paper titled, “Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.”

Immune checkpoint blockade using monoclonal antibodies (mAbs) targeting programmed cell death protein 1 (PD-1) provides long-term clinical benefits to nearly 40% of patients with advanced melanoma, the authors wrote. Research suggests that communities of bacteria and viruses in the intestines can affect the immune system and its response to chemotherapy and immunotherapy, including anti-PD-1 therapy. Interestingly, they continued, “the composition of the gut microbiota correlates with anti–PD-1 efficacy in preclinical models and cancer patients.” And previous studies have shown that tumor-bearing mice that do not respond to immunotherapy drugs can start to respond if they receive certain gut microorganisms from mice that responded to the drugs. However, there are still questions, the team acknowledged. “Although multiple studies have reported that a favorable gut microbiome is associated with response to anti–PD-1 in cancer patients, its precise composition is not yet fully understood.”

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