Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients

V. Gopalakrishnan, C. N. Spencer, L. Nezi, A. Reuben, M. C. Andrews, T. V. Karpinets, P. A. Prieto, D. Vicente, K. Hoffman, S. C. Wei, A. P. Cogdill, L. Zhao, C. W. Hudgens, D. S. Hutchinson, T. Manzo, M. Petaccia De Macedo, T. Cotechini, T. Kumar, W. S. Chen, S. M. ReddyR. Szczepaniak Sloane, J. Galloway-Pena, H. Jiang, P. L. Chen, E. J. Shpall, K. Rezvani, A. M. Alousi, R. F. Chemaly, S. Shelburne, L. M. Vence, P. C. Okhuysen, V. B. Jensen, A. G. Swennes, F. McAllister, E. Marcelo Riquelme Sanchez, Y. Zhang, E. Le Chatelier, L. Zitvogel, N. Pons, J. L. Austin-Breneman, L. E. Haydu, E. M. Burton, J. M. Gardner, E. Sirmans, J. Hu, A. J. Lazar, T. Tsujikawa, A. Diab, H. Tawbi, I. C. Glitza, W. J. Hwu, S. P. Patel, S. E. Woodman, R. N. Amaria, M. A. Davies, J. E. Gershenwald, P. Hwu, J. E. Lee, J. Zhang, L. M. Coussens, Z. A. Cooper, P. A. Futreal, C. R. Daniel, N. J. Ajami, J. F. Petrosino, M. T. Tetzlaff, P. Sharma, J. P. Allison, R. R. Jenq, J. A. Wargo

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915 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)97-103
Number of pages7
JournalScience
Volume359
Issue number6371
DOIs
StatePublished - Jan 5 2018
Externally publishedYes

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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., ... Wargo, J. A. (2018). Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science, 359(6371), 97-103. https://doi.org/10.1126/science.aan4236