| Literature DB >> 29097493 |
V Gopalakrishnan1,2, C N Spencer2,3, L Nezi3, A Reuben1, M C Andrews1, T V Karpinets3, P A Prieto1, D Vicente1, K Hoffman4, S C Wei5, A P Cogdill1,5, L Zhao3, C W Hudgens6, D S Hutchinson7, T Manzo3, M Petaccia de Macedo6, T Cotechini8, T Kumar3, W S Chen9, S M Reddy10, R Szczepaniak Sloane1, J Galloway-Pena11, H Jiang1, P L Chen9, E J Shpall12, K Rezvani12, A M Alousi12, R F Chemaly11, S Shelburne3,11, L M Vence5, P C Okhuysen11, V B Jensen13, A G Swennes7, F McAllister14, E Marcelo Riquelme Sanchez14, Y Zhang14, E Le Chatelier15, L Zitvogel16, N Pons15, J L Austin-Breneman1, L E Haydu1, E M Burton1, J M Gardner1, E Sirmans17, J Hu18, A J Lazar6,9, T Tsujikawa8, A Diab17, H Tawbi17, I C Glitza17, W J Hwu17, S P Patel17, S E Woodman17, R N Amaria17, M A Davies17, J E Gershenwald1, P Hwu17, J E Lee1, J Zhang3, L M Coussens8, Z A Cooper1,3, P A Futreal3, C R Daniel4,2, N J Ajami7, J F Petrosino7, M T Tetzlaff6,9, P Sharma5,19, J P Allison5, R R Jenq3, J A Wargo20,3.
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.Entities:
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Year: 2017 PMID： 29097493 PMCID： PMC5827966 DOI： 10.1126/science.aan4236
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728