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 fecal microbiota (FMT) transplantation 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 the increased rate abundance previously shown to be associated with the response to anti-PD-1, increased 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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Programmed anti-cell death protein 1 (PD-1) therapy offers long-term clinical benefits for patients with advanced melanoma. The composition of the intestinal microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti-PD-1 can be overcome by altering the intestinal microbiota, this clinical trial evaluated the safety and efficacy of the transponder-derived fecal microbiota (FMT) transplant together with anti-PD-1 in patients with PD- 1 – Refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 out of 15 patients and induced rapid and durable microbiota disturbance. Respondents exhibited a greater abundance of taxa that were previously associated with the response to anti-PD-1, increased CD8+ T cell activation and decreased frequency of myeloid cells that express interleukin-8. Respondents had distinct proteomic and metabolomic signatures, and analyzes of the trans-kingdom network confirmed that the intestinal microbiome regulated these changes. Collectively, our results show that FMT and anti-PD-1 changed the intestinal microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of advanced melanoma PD-1.