New fecal microbiota for cancer patients
The composition of the intestinal microbiome influences the response of cancer patients to immunotherapies. Baruch et al. and Davar et al. report the first human clinical trials to test whether a fecal microbiota (FMT) transplant can affect how patients with metastatic melanoma respond to anti-PD-1 immunotherapy (see Woelk and Snyder’s Perspective). Both studies found evidence of clinical benefit in a subset of treated patients. This included an increase in the abundance of taxa previously shown to be associated with the response to anti-PD-1, an increase in CD8+ Activation of T cells and decreased frequency of myeloid cells that express interleukin-8, which are involved in immunosuppression. These studies provide proof of concept evidence for the ability of FMT to affect the response of immunotherapy in cancer patients.
Science, this problem p. 602, p. 595; see also p. 573
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The intestinal microbiome has been shown to influence tumor response to anti-PD-1 immunotherapy (programmed cell death-1) in preclinical mouse models and observational patient cohorts. However, 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 assess the safety and viability of fecal microbiota transplantation (FMT) and re-induction of anti-PD-1 immunotherapy in 10 patients with metastatic melanoma refractory to anti-PD-1. We observed clinical responses in three patients, including two partial responses and a complete response. Notably, treatment with FMT has been associated with favorable changes in the infiltrates of immune cells and gene expression profiles both in the intestinal lamina propria and in the tumor microenvironment. These initial findings have implications for the modulation of the intestinal microbiota in the treatment of cancer.