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 a reduced frequency of interleukin-8-expressing myeloid cells, involved in immunosuppression. 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
Abstract
Anti-programmed 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, the clinical trial examined the safety and efficacy of reactive-derived fecal microbiota transplantation (FMT) with anti-PD-1 in patients with PD-1 assessed –Refractory melanoma. This combination is well tolerated, provides clinical benefit in 6 of 15 patients and causes rapid and lasting disruption by microbiota. Respondents showed an increased amount of taxa previously shown to be associated with response to anti-PD-1, increased CD8+ T cell activation, and reduced frequency of interleukin-8-expressing myeloid cells. Respondents had clear proteomic and metabolomic signatures, and analysis of the transkingdom network confirmed that the intestinal microbiome regulates these changes. Collectively, our findings show that FMT and anti-PD-1 altered the intestinal microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of advanced melanoma of PD-1.