Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.
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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.
author list (cited authors)
Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., ... Wargo, J. A.
complete list of authors
Gopalakrishnan, V||Spencer, CN||Nezi, L||Reuben, A||Andrews, MC||Karpinets, TV||Prieto, PA||Vicente, D||Hoffman, K||Wei, SC||Cogdill, AP||Zhao, L||Hudgens, CW||Hutchinson, DS||Manzo, T||Petaccia de Macedo, M||Cotechini, T||Kumar, T||Chen, WS||Reddy, SM||Szczepaniak Sloane, R||Galloway-Pena, J||Jiang, H||Chen, PL||Shpall, EJ||Rezvani, K||Alousi, AM||Chemaly, RF||Shelburne, S||Vence, LM||Okhuysen, PC||Jensen, VB||Swennes, AG||McAllister, F||Marcelo Riquelme Sanchez, E||Zhang, Y||Le Chatelier, E||Zitvogel, L||Pons, N||Austin-Breneman, JL||Haydu, LE||Burton, EM||Gardner, JM||Sirmans, E||Hu, J||Lazar, AJ||Tsujikawa, T||Diab, A||Tawbi, H||Glitza, IC||Hwu, WJ||Patel, SP||Woodman, SE||Amaria, RN||Davies, MA||Gershenwald, JE||Hwu, P||Lee, JE||Zhang, J||Coussens, LM||Cooper, ZA||Futreal, PA||Daniel, CR||Ajami, NJ||Petrosino, JF||Tetzlaff, MT||Sharma, P||Allison, JP||Jenq, RR||Wargo, JA