학술논문
Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients
Document Type
Academic Journal
Author
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.
Source
Science. Jan 05, 2018 359(6371):97-103
Subject
Language
English
ISSN
0036-8075
Abstract
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 (n = 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 (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 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.