Baruch et al. reported that fecal microbiota transplantation (FMT) from complete responder donors and re-induction of anti-PD-1 therapy in ten anti-PD-1-refractory metastatic melanoma patients was safe, feasible, and potentially effective. Three recipients (all from one donor) demonstrated clinical responses, including one complete response and two partial responses. Tumor samples demonstrated upregulation of multiple immune-related gene sets, such as IFNγ-mediated signaling pathway, T cell activation, MHC Class II protein complex, dendritic cell differentiation, and T helper 1 type immune response, after FMT treatment.
Contributed by Shishir Pant
ABSTRACT: The gut microbiome has been shown to influence the response of tumors to anti-PD-1 immunotherapy in pre-clinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. Here we performed a phase I clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and re-induction of anti-PD-1 immunotherapy in ten patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. Together, these early findings have important implications for modulating the gut microbiota in cancer treatment.