Fecal microbiota transplant promotes response in patients with immune-refractory melanoma



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New fecal microbiota for cancer patients

The composition of the gut microbiome influences the response of cancer patients to immunotherapy. Baruch et al. and Davar et al. report the first clinical trials in humans to test whether fecal microbiota transplantation (FMT) can affect how patients with metastatic melanoma respond to anti-PD-1 immunotherapy (see perspective from Woelk and Snyder) . Both studies observed evidence of clinical benefit in a subset of treated patients. This included an increase in the abundance of taxa previously associated with a response to anti-PD-1, an increase in CD8.+ Activation of T lymphocytes and decrease in the frequency of myeloid cells expressing interleukin 8, involved in immunosuppression. These studies provide proof of concept for the ability of FMT to affect the immunotherapeutic response in cancer patients.

Science, this issue p. 602, p. 595; see also p. 573

Abstract

The gut microbiome has been shown to influence the response of tumors to anti – PD-1 (programmed cell death – 1) immunotherapy in preclinical mouse models and observational patient cohorts. However, modulation of the gut microbiota in cancer patients has not been studied in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti-PD-1 immunotherapy in 10 patients with anti-metastatic melanoma. – PD-1 – refractory. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT has been associated with favorable changes in immune cell infiltrates and gene expression profiles both in the intestinal lamina propria and in the tumor microenvironment. These early findings have implications for the modulation of the gut microbiota in the treatment of cancer.

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