Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement Access content directly
Journal Articles Science Year : 2018

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

V. Gopalakrishnan
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C. N. Spencer
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L. Nezi
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A. Reuben
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P. A. Prieto
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D. Vicente
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L. Zhao
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T. Manzo
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T. Kumar
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W. S. Chen
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H. Jiang
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P. L. Chen
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E. J. Shpall
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K. Rezvani
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A. M. Alousi
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S. Shelburne
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L. M. Vence
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V. B. Jensen
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Y. Zhang
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Emmanuelle Le Chatelier
Nicolas Pons
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L. E. Haydu
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E. M. Burton
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A. J. Lazar
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J. E. Lee
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J. Zhang
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Z. A. Cooper
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R. R. Jenq
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J. A. Wargo
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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.
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Dates and versions

hal-02629159 , version 1 (02-04-2024)

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V. Gopalakrishnan, C. N. Spencer, L. Nezi, A. Reuben, M. C. Andrews, et al.. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science, 2018, 359 (6371), pp.97-103. ⟨10.1126/science.aan4236⟩. ⟨hal-02629159⟩
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