New fecal microbiota for cancer patients
The composition of the gut microbiome influences the response of cancer patients to immunotherapies. Baruch et al. and Davar et al. report initial clinical studies in humans to test whether fecal microbiota transplantation (FMT) can affect how patients with metastatic melanoma respond to anti-PD-1 immunotherapy (see Woelk and Snyder’s perspective). In both studies, clinical benefit was seen in a subgroup of treated patients. This included increased abundance of taxa previously shown to be related to response to anti-PD-1, increased CD8+ T cell activation and decreased frequency of myeloid cells expressing interleukin-8 involved in immunosuppression. These studies provide proof-of-concept evidence for the ability of FMT to affect immunotherapy response in cancer patients.
Science, this issue p. 602, p. 595; see also p. 573
Abstract
Anti-programmed cell death protein 1 (PD-1) therapy offers long-term clinical benefits for patients with advanced melanoma. Gut microbiota composition 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 gut microbiota, this clinical study evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) along 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 caused rapid and lasting microbiota disruption. Responders showed an increased abundance of taxa previously shown to be associated with response to anti-PD-1, increased CD8+ T cell activation and decreased frequency of myeloid cells expressing interleukin-8. Responders had different proteomic and metabolomic signatures, and transkingdom network analyzes confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti-PD-1 altered the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma.