Volume 19, Issue 10, Pages (October 2017)

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Volume 19, Issue 10, Pages 848-855 (October 2017) Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients Arthur E. Frankel, Laura A. Coughlin, Jiwoong Kim, Thomas W. Froehlich, Yang Xie, Eugene P. Frenkel, Andrew Y. Koh Neoplasia Volume 19, Issue 10, Pages 848-855 (October 2017) DOI: 10.1016/j.neo.2017.08.004 Copyright © 2017 The Authors Terms and Conditions

Figure 1 Study schema. Neoplasia 2017 19, 848-855DOI: (10.1016/j.neo.2017.08.004) Copyright © 2017 The Authors Terms and Conditions

Figure 2 MSS identifies specific bacterial species that are enriched in the gut microbiomes of melanoma patients who are responding to ICT therapy. Relative abundance of gut bacterial taxa as determined by MetaPhlAn analysis of MSS data generated from fecal specimens collected from melanoma patients prior to receiving ipilimumab/nivolumab, pembrolizumab, ipilimumab alone, or nivolumab alone. Differential taxonomic abundance was analyzed by linear discriminate analysis coupled with effect size measurements (LEfSe) projected as a histogram (A, C and E) or cladrogram (B, D and F). All listed bacterial groups were significantly (P<.05, Kruskal-Wallis test) enriched for their respective groups (responder versus progressive). Neoplasia 2017 19, 848-855DOI: (10.1016/j.neo.2017.08.004) Copyright © 2017 The Authors Terms and Conditions

Figure 3 Unbiased metabolomics analysis of stool metabolites from adult melanoma patients prior to treatment with ICT. UPLC-MS–based global profiling of metabolites in feces of adult melanoma patients receiving immune checkpoint inhibitor therapy (n=39). Data were log transformed and mean centered. Venn diagrams of metabolites (A) significantly increased or (B) decreased when comparing the ICT responder group versus the progressive group for all ICTs, IN only, and P only. The heat maps show the normalized relative abundances of stool metabolites comparing responders to those with progressive disease for (C) all ICTs, (D) IN only, and (E) P only (q<0.05, unpaired t test with Welch's correction followed by false discovery rate correction). Orange colors indicate relative abundance increase, and blue indicates relative abundances decrease (responders:progressive, log2 transformed). Neoplasia 2017 19, 848-855DOI: (10.1016/j.neo.2017.08.004) Copyright © 2017 The Authors Terms and Conditions