New fecal microbiota for cancer patients
The composition of the intestinal microbiome influences the response of cancer patients to immunotherapies. Baruch et al. in Davar et al. reports first-in-human clinical trials to test whether fecal microbiota transplantation (FMT) may affect how metastatic melanoma patients respond to anti-PD-1 immunotherapy (see the Perspective of Cloud and Snyder). Both studies demonstrated clinical benefit in a subgroup of treated patients. This included an increased amount of taxa previously shown to be associated with response to anti-PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells, involved in immune suppression. These studies provide conceptual evidence for the ability of FMT to influence immunotherapy response in cancer patients.
Science, this issue p. 602, p. 595; see also p. 573
Summary
The intestinal microbiome has been shown to influence the response of tumors to anti-PD-1 (programmed cell death – 1) immunotherapy in preclinical mouse models and observing patient groups. However, the modulation of the intestinal microbiota in cancer patients has not been investigated in clinical trials. In this study, we conducted a phase 1 clinical trial to determine the safety and feasibility of fecal microbiota transplantation (FMT) and re-induction of anti-PD-1 immunotherapy in 10 patients with anti-PD-1 refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. In particular, treatment with FMT has been associated with favorable changes in immune cell infiltrates and gene expression profiles in both the intestinal lamina propria and the microenvironment of the tumor. These early findings have implications for the modulation of the intestinal microbiota in cancer treatment.