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Title:
Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis | Nature Communications
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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headline:Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis
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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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