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

Vancheswaran Gopalakrishnan, Luigi Nezi, Alexandre Reuben, Miles Cameron Andrews, Tatiana V. Karpinets, Peter A. Prieto, Diego A. Vicente, Kristi Louise Hoffman, Spencer C. Wei, Alexandria P. Cogdill, Courtney W. Hudgens, Diane S. Hutchinson, Teresa Manzo, Mariana Petaccia de Macêdo, Tiziana Cotechini, Tapsi Kumar, Sangeetha Meda Reddy, Robert A. Szczepaniak Sloane, Jessica Galloway-Peña, Hong Jiang, P. L. Chen, Elizabeth J. Shpall, Katayoun Rezvani, Amin Majid Alousi, Roy F. Chemaly, Samuel A. Shelburne, Luis M. Vence, Pablo C. Okhuysen, Vanessa Behrana Jensen, Alton G. Swennes, Florencia M. McAllister, Erick Marcelo Riquelme, Yexi Zhang, Emmanuelle Le Chatelier, Laurence Zitvogel, Nicolas Pons, Jacob L. Austin-Breneman, Lauren Elaine Haydu, Elizabeth M. Burton, Julie M. Gardner, Elizabeth Sirmans, Jiemiao Hu, Alexander J. Lazar, Takahiro Tsujikawa, Adi K. Diab, Hussein A. Tawbi, Isabella C. Glitza, Wen‐Jen Hwu, Sapna Pradyuman Patel, Scott Eric Woodman, Rodabe Navroze Amaria, Michael A. Davies, Jeffrey E. Gershenwald, Patrick Hwu, J. Zhang, Lisa M. Coussens, Zachary Aaron Cooper, P. Andrew Futreal, Carrie R. Daniel, Nadim J. Ajami, Joseph F. Petrosino, Michael T. Tetzlaff, Padmanee Sharma, James Patrick Allison, Robert R. Jenq, Jennifer Ann Wargo

Science · 2017 · 4,879 citationsOpen access

Abstract

Good bacteria help fight cancer Resident gut bacteria can affect patient responses to cancer immunotherapy (see the Perspective by Jobin). Routy et al. show that antibiotic consumption is associated with poor response to immunotherapeutic PD-1 blockade. They profiled samples from patients with lung and kidney cancers and found that nonresponding patients had low levels of the bacterium Akkermansia muciniphila . Oral supplementation of the bacteria to antibiotic-treated mice restored the response to immunotherapy. Matson et al. and Gopalakrishnan et al. studied melanoma patients receiving PD-1 blockade and found a greater abundance of “good” bacteria in the guts of responding patients. Nonresponders had an imbalance in gut flora composition, which correlated with impaired immune cell activity. Thus, maintaining healthy gut flora could help patients combat cancer. Science , this issue p. 91 , p. 104 , p. 97 ; see also p. 32

Cite this paper

Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., Prieto, P. A., Vicente, D. A., Hoffman, K. L., Wei, S. C., Cogdill, A. P., Zhao, L., Hudgens, C. W., Hutchinson, D. S., Manzo, T., Macêdo, M. P. de, Cotechini, T., Kumar, T., Chen, W. S., … Wargo, J. A. (2017). Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science, 359(6371), 97–103. https://doi.org/10.1126/science.aan4236

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