送交者: iamback 于 2018-02-11 15:20:01
Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.
Gopalakrishnan V1,2, Spencer CN2,3, Nezi L3, Reuben A1, Andrews MC1, Karpinets TV3, Prieto PA1, Vicente D1, Hoffman K4, Wei SC5, Cogdill AP1,5, Zhao L3, Hudgens CW6, Hutchinson DS7, Manzo T3, Petaccia de Macedo M6, Cotechini T8, Kumar T3, Chen WS9, Reddy SM10, Szczepaniak Sloane R1, Galloway-Pena J11, Jiang H1, Chen PL9, Shpall EJ12, Rezvani K12, Alousi AM12, Chemaly RF11, Shelburne S3,11, Vence LM5, Okhuysen PC11, Jensen VB13, Swennes AG7, McAllister F14, Marcelo Riquelme Sanchez E14, Zhang Y14, Le Chatelier E15, Zitvogel L16, Pons N15, Austin-Breneman JL1, Haydu LE1, Burton EM1, Gardner JM1, Sirmans E17, Hu J18, Lazar AJ6,9, Tsujikawa T8, Diab A17, Tawbi H17, Glitza IC17, Hwu WJ17, Patel SP17, Woodman SE17, Amaria RN17, Davies MA17, Gershenwald JE1, Hwu P17, Lee JE1, Zhang J3, Coussens LM8, Cooper ZA1,3, Futreal PA3, Daniel CR4,2, Ajami NJ7, Petrosino JF7, Tetzlaff MT6,9, Sharma P5,19, Allison JP5, Jenq RR3, Wargo JA20,3.
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.
Science. 2018 Jan 5;359(6371):97-103. doi: 10.1126/science.aan4236. Epub 2017 Nov 2.
Copyright © 2000 - 2005 rainbowplan.org