Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients
V. Gopalakrishnan
(1)
,
C. N. Spencer
(1)
,
L. Nezi
(1)
,
A. Reuben
(1)
,
M. C. Andrews
(1)
,
T. V. Karpinets
(1)
,
P. A. Prieto
(1)
,
D. Vicente
(1)
,
K. Hoffman
(2)
,
S. C. Wei
(2)
,
A. P. Cogdill
(1)
,
L. Zhao
(1)
,
C. W. Hudgens
(1)
,
D. S. Hutchinson
(3)
,
T. Manzo
(1)
,
M. Petaccia de Macedo
(1)
,
T. Cotechini
(4)
,
T. Kumar
(1)
,
W. S. Chen
(1)
,
S. M. Reddy
(5)
,
R. Szczepaniak Sloane
(1)
,
J. Galloway-Pena
(1)
,
H. Jiang
(1)
,
P. L. Chen
(1)
,
E. J. Shpall
(1)
,
K. Rezvani
(1)
,
A. M. Alousi
(1)
,
R. F. Chemaly
(1)
,
S. Shelburne
(1)
,
L. M. Vence
(1)
,
P. C. Okhuysen
(1)
,
V. B. Jensen
(1)
,
A. G. Swennes
(3)
,
F. Mcallister
(1)
,
E. Marcelo Riquelme Sanchez
(1)
,
Y. Zhang
(1)
,
Emmanuelle Le Chatelier
(6)
,
L. Zitvogel
(7, 8)
,
Nicolas Pons
(6)
,
J. L. Austin-Breneman
(1)
,
L. E. Haydu
(1)
,
E. M. Burton
(1)
,
J. M. Gardner
(1)
,
E. Sirmans
(9)
,
J. Hu
(9)
,
A. J. Lazar
(1)
,
T. Tsujikawa
(4)
,
A. Diab
(9)
,
H. Tawbi
(9)
,
I. C. Glitza
(9)
,
W. J. Hwu
(9)
,
S. P. Patel
(9)
,
S. E. Woodman
(9)
,
R. N. Amaria
(9)
,
M. A. Davies
(9)
,
J. E. Gershenwald
(1)
,
P. Hwu
(9)
,
J. E. Lee
(1)
,
J. Zhang
(1)
,
L. M. Coussens
(4)
,
Z. A. Cooper
(1)
,
P. A. Futreal
(1)
,
C. R. Daniel
(2, 1)
,
N. J. Ajami
(3)
,
J. F. Petrosino
(3)
,
M. T. Tetzlaff
(1)
,
Pradeep Sharma
(1)
,
J. P. Allison
(3)
,
R. R. Jenq
(1)
,
J. A. Wargo
(1)
1
University of Texas
2 University of Texas M. D. Anderson Cancer Center
3 Department of Molecular Virology and Microbiology
4 University of Oregon
5 Department of breast medical oncology
6 MetaGenoPolis
7 IGR - Institut Gustave Roussy
8 UMR 1015 - Immunologie des tumeurs et immunothérapie
9 Department of Melanoma Medical Oncology
2 University of Texas M. D. Anderson Cancer Center
3 Department of Molecular Virology and Microbiology
4 University of Oregon
5 Department of breast medical oncology
6 MetaGenoPolis
7 IGR - Institut Gustave Roussy
8 UMR 1015 - Immunologie des tumeurs et immunothérapie
9 Department of Melanoma Medical Oncology
Emmanuelle Le Chatelier
- Fonction : Auteur
- PersonId : 737756
- IdHAL : emmanuelle-le-chatelier
- ORCID : 0000-0002-2724-0536
J. A. Wargo
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- Fonction : Auteur correspondant
- PersonId : 1070791
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Résumé
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.