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Gopalakrishnan, V; Spencer, C N; Nezi, L; Reuben, A; Andrews, M C; Karpinets, T V; Prieto, P A; Vicente, D; Hoffman, K; Wei, S C; Cogdill, A P; Zhao, L; Hudgens, C W; Hutchinson, D S; Manzo, T; Petaccia de Macedo, M; Cotechini, T; Kumar, T; Chen, W S; Reddy, S M; Szczepaniak Sloane, R; Galloway-Pena, J; Jiang, H; Chen, P L; Shpall, E J; Rezvani, K; Alousi, A M; Chemaly, R F; Shelburne, S; Vence, L M; Okhuysen, P C; Jensen, V B; Swennes, A G; McAllister, F; Marcelo Riquelme Sanchez, E; Zhang, Y; Le Chatelier, E; Zitvogel, L; Pons, N; Austin-Breneman, J L; Haydu, L E; Burton, E M; Gardner, J M; Sirmans, E; Hu, J; Lazar, A J; Tsujikawa, T; Diab, A; Tawbi, H; Glitza, I C; Hwu, W J; Patel, S P; Woodman, S E; Amaria, R N; Davies, M A; Gershenwald, J E; Hwu, P; Lee, J E; Zhang, J; Coussens, L M; Cooper, Z A; Futreal, P A; Daniel, C R; Ajami, N J; Petrosino, J F; Tetzlaff, M T; Sharma, P; Allison, J P; Jenq, R R; Wargo, J A
Science (American Association for the Advancement of Science), 01/2018, Volume: 359, Issue: 6371Journal Article
Preclinical mouse models suggest 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 anti-programmed cell death 1 protein (PD-1) immunotherapy ( = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples ( = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity ( < 0.01) and relative abundance of bacteria of the Ruminococcaceae family ( < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor 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 the treatment of melanoma patients with immune checkpoint inhibitors.
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