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samn, patients, colitis, pubmed, article, google, scholar, microbiota, cas, intestinal, ptc, otus, microbial, modules, fig, analysis, inflammation, abundance, patient, nature, ipilimumab, cancer, samples, central, york, ctla, development, polyamine, phylum, transport, biosynthesis, sequencing, supplementary, relative, bacteroidetes, bacterial, melanoma, composition, blockade, faecal, score, risk, treatment, study, cells, performed, test, system, usa, microbiome,

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• The Microbiome in Advanced Melanoma: Where Are We Now?

Schema {🗺️}

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         headline:Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis
         description:The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota’s composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy. A subset of cancer patients treated with immune checkpoint blockade develops colitis. Here the authors show that lower abundance of Bacteroidetes and vitamin B biosynthetic modules in fecal samples of melanoma patients can predict their susceptibility to colitis following anti-CTLA-4 treatment.
         datePublished:2016-02-02T00:00:00Z
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      headline:Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis
      description:The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota’s composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy. A subset of cancer patients treated with immune checkpoint blockade develops colitis. Here the authors show that lower abundance of Bacteroidetes and vitamin B biosynthetic modules in fecal samples of melanoma patients can predict their susceptibility to colitis following anti-CTLA-4 treatment.
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            name:Infectious Diseases Service, Memorial Sloan Kettering Cancer Center
            address:
               name:Department of Medicine, Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, USA
               type:PostalAddress
            type:Organization
            name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center
            address:
               name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, USA
               type:PostalAddress
            type:Organization
            name:Weill Cornell Graduate School of Medical Sciences of Cornell University
            address:
               name:Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, USA
               type:PostalAddress
            type:Organization
      name:Margaret K. Callahan
      affiliation:
            name:Weill Cornell Medical College
            address:
               name:Weill Cornell Medical College, New York, USA
               type:PostalAddress
            type:Organization
            name:Melanoma and Immunotherapy Service, Memorial Sloan Kettering Cancer Center
            address:
               name:Department of Medicine, Melanoma and Immunotherapy Service, Memorial Sloan Kettering Cancer Center, New York, USA
               type:PostalAddress
            type:Organization
      name:Boyu Ren
      affiliation:
            name:Harvard School of Public Health
            address:
               name:Department of Biostatistics, Harvard School of Public Health, Boston, USA
               type:PostalAddress
            type:Organization
      name:Raya Khanin
      affiliation:
            name:Computational Biology Program, Sloan-Kettering Institute
            address:
               name:Computational Biology Program, Sloan-Kettering Institute, New York, USA
               type:PostalAddress
            type:Organization
      name:Agnes Viale
      affiliation:
            name:Genomics Core Laboratory, Sloan-Kettering Institute
            address:
               name:Genomics Core Laboratory, Sloan-Kettering Institute, New York, USA
               type:PostalAddress
            type:Organization
      name:Lilan Ling
      affiliation:
            name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center
            address:
               name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, USA
               type:PostalAddress
            type:Organization
      name:Daniel No
      affiliation:
            name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center
            address:
               name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, USA
               type:PostalAddress
            type:Organization
      name:Asia Gobourne
      affiliation:
            name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center
            address:
               name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, USA
               type:PostalAddress
            type:Organization
      name:Eric Littmann
      affiliation:
            name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center
            address:
               name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, USA
               type:PostalAddress
            type:Organization
      name:Curtis Huttenhower
      affiliation:
            name:Harvard School of Public Health
            address:
               name:Department of Biostatistics, Harvard School of Public Health, Boston, USA
               type:PostalAddress
            type:Organization
            name:Microbial Systems and Communities, Genome Sequencing and Analysis Program, The Broad Institute
            address:
               name:Microbial Systems and Communities, Genome Sequencing and Analysis Program, The Broad Institute, Cambridge, USA
               type:PostalAddress
            type:Organization
      name:Eric G. Pamer
      affiliation:
            name:Infectious Diseases Service, Memorial Sloan Kettering Cancer Center
            address:
               name:Department of Medicine, Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, USA
               type:PostalAddress
            type:Organization
            name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center
            address:
               name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, USA
               type:PostalAddress
            type:Organization
            name:Immunology Program, Sloan-Kettering Institute
            address:
               name:Immunology Program, Sloan-Kettering Institute, New York, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Jedd D. Wolchok
      affiliation:
            name:Weill Cornell Medical College
            address:
               name:Weill Cornell Medical College, New York, USA
               type:PostalAddress
            type:Organization
            name:Melanoma and Immunotherapy Service, Memorial Sloan Kettering Cancer Center
            address:
               name:Department of Medicine, Melanoma and Immunotherapy Service, Memorial Sloan Kettering Cancer Center, New York, USA
               type:PostalAddress
            type:Organization
            name:Immunology Program, Sloan-Kettering Institute
            address:
               name:Immunology Program, Sloan-Kettering Institute, New York, USA
               type:PostalAddress
            type:Organization
            name:Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center
            address:
               name:Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Medicine, Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, USA
      name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, USA
      name:Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, USA
      name:Weill Cornell Medical College, New York, USA
      name:Department of Medicine, Melanoma and Immunotherapy Service, Memorial Sloan Kettering Cancer Center, New York, USA
      name:Department of Biostatistics, Harvard School of Public Health, Boston, USA
      name:Computational Biology Program, Sloan-Kettering Institute, New York, USA
      name:Genomics Core Laboratory, Sloan-Kettering Institute, New York, USA
      name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, USA
      name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, USA
      name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, USA
      name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, USA
      name:Department of Biostatistics, Harvard School of Public Health, Boston, USA
      name:Microbial Systems and Communities, Genome Sequencing and Analysis Program, The Broad Institute, Cambridge, USA
      name:Department of Medicine, Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, USA
      name:Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, USA
      name:Immunology Program, Sloan-Kettering Institute, New York, USA
      name:Weill Cornell Medical College, New York, USA
      name:Department of Medicine, Melanoma and Immunotherapy Service, Memorial Sloan Kettering Cancer Center, New York, USA
      name:Immunology Program, Sloan-Kettering Institute, New York, USA
      name:Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, USA

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