Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients

TLDR

Anti‑PD‑1 therapy confers long‑term benefits in advanced melanoma, and gut microbiota composition has been linked to anti‑PD‑1 efficacy in preclinical models and patients. The study aimed to determine whether modifying the gut microbiota could overcome resistance to anti‑PD‑1 therapy in melanoma patients. A clinical trial administered responder‑derived fecal microbiota transplantation together with anti‑PD‑1 to evaluate safety and efficacy in patients with PD‑1‑refractory melanoma. The combination was well tolerated, produced clinical benefit in 6 of 15 patients, and induced rapid, durable microbiota perturbation with increased taxa associated with anti‑PD‑1 response and CD8 T‑cell activity.

Abstract

Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8