Tumor and gut biopsies from refractory metastatic melanoma patients before and after treatment with fecal microbiota transplantation (FMT) and anti-PD-1 re-induction (Baruch et al, Science 2020)

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 patients with anti-PD-1-refractory metastatic melanoma. FMT donors were two metastatic melanoma patients who achieved a durable complete response. FMT recipient patients were metastatic melanoma patients who failed at least one anti-PD-1 line of treatment. Each recipient patient received FMT implants from only one of the two donors. FMT was conducted by both colonoscopy and oral ingestion of stool capsules, followed by anti-PD-1 re-treatment (Nivolumab, BMS). Recipient patients underwent pre- and post-treatment stool sampling, tissue biopsy of both gut and tumor, and total body imaging. Clinical responses were observed 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. Overall design: Biopsies from the sigmoid colon (large bowel, gut) and from remote (non-GI) tumor metastasis were collected from available treatment recipient patient (n=9) before initiation of treatment (day 0). Repeated sigmoid colon biopsies were collected on day 31 of treatment. Repeated tumor biopsies, either from the same metastasis as the baseline sample or an adjunct metastasis in a same organ, were collected on day 65. Overall, each patient had two gut biopsies and two tumor biopsies. All biopsies underwent RNA sequencing to assess for potential dynamics of the immune system in response to treatment