ena-STUDY-MD ANDERSON CANCER CENTER-04-10-2017-22:22:35:492-108
Gut microbiome impacts response to PD-1 immunotherapy in melanoma patients
Pre-clinical mouse models have suggested that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy, however this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing PD-1 blockade immunotherapy (n=112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders (R) versus non-responders (NR). Analysis of patient fecal microbiome samples (n=43, 30R, 13NR) showed significantly higher alpha diversity (p<0.01) and relative abundance of Ruminococcaceae bacteria (p<0.01) in R. Metagenomic studies revealed functional differences in gut bacteria in R including enrichment of anabolic pathways. Immune profiling found enhanced systemic and anti-tumor immunity in responding patients with a favorable gut microbiome, as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for treatment with immune checkpoint blockade in melanoma.
Pre-clinical mouse models have suggested that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy, however this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing PD-1 blockade immunotherapy (n=112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders (R) versus non-responders (NR). Analysis of patient fecal microbiome samples (n=43, 30R, 13NR) showed significantly higher alpha diversity (p<0.01) and relative abundance of Ruminococcaceae bacteria (p<0.01) in R. Metagenomic studies revealed functional differences in gut bacteria in R including enrichment of anabolic pathways. Immune profiling found enhanced systemic and anti-tumor immunity in responding patients with a favorable gut microbiome, as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for treatment with immune checkpoint blockade in melanoma.