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Fecal Transplant May Counter Anti-PD-1 Resistance in Melanoma

TUESDAY, Feb. 23, 2021 -- Fecal microbiota transplantation (FMT) together with anti-programmed cell death protein 1 (PD-1) therapy possibly may alter the gut microbiome and overcome resistance to anti-PD-1 in some patients with melanoma, according to a study published in the Feb. 5 issue of Science.

Noting that the composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients, Diwakar Davar, M.D., from the University of Pittsburgh, and colleagues assessed the safety and efficacy of responder-derived FMT together with anti-PD-1 in 15 patients with PD-1-refractory melanoma.

The researchers found that the combination was well tolerated, provided clinical benefit in six patients, and induced rapid and durable perturbation of microbiota. In responders, an abundance of taxa increased that were previously shown to be associated with response to anti-PD-1, CD8+ T cell activation increased, and the frequency of interleukin-8-expressing myeloid cells was reduced. Distinct proteomic and metabolomic signatures were seen for responders, and confirmation that the gut microbiome regulated these changes was provided by transkingdom network analyses.

"We expect that future studies will identify which groups of bacteria in the gut are capable of converting patients who do not respond to immunotherapy drugs into patients who do respond," a coauthor said in a statement. "If researchers can identify which microorganisms are critical for the response to immunotherapy, then it may be possible to deliver these organisms directly to patients who need them, without requiring a fecal transplant."

Several authors disclosed financial ties to pharmaceutical companies, including Merck MSD, which funded the clinical trial.

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