title: Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis.
abstract: 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.
authors.affiliation: Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.|Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.|Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, New York 10065, USA.
authors.forename: Krista
authors.initials: K
authors.lastname: Dubin
authors.affiliation: Weill Cornell Medical College, New York, New York 10065, USA.|Melanoma and Immunotherapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Margaret K
authors.initials: MK
authors.lastname: Callahan
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
authors.forename: Boyu
authors.initials: B
authors.lastname: Ren
authors.affiliation: Computational Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA.
authors.forename: Raya
authors.initials: R
authors.lastname: Khanin
authors.affiliation: Genomics Core Laboratory, Sloan-Kettering Institute, New York, New York 10065, USA.
authors.forename: Agnes
authors.initials: A
authors.lastname: Viale
authors.affiliation: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Lilan
authors.initials: L
authors.lastname: Ling
authors.affiliation: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: No
authors.affiliation: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Asia
authors.initials: A
authors.lastname: Gobourne
authors.affiliation: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Littmann
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.|Microbial Systems and Communities, Genome Sequencing and Analysis Program, The Broad Institute, Cambridge, Massachusetts 02142, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Huttenhower
authors.affiliation: Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.|Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.|Immunology Program, Sloan-Kettering Institute, New York, New York 10065, USA.
authors.forename: Eric G
authors.initials: EG
authors.lastname: Pamer
authors.affiliation: Weill Cornell Medical College, New York, New York 10065, USA.|Melanoma and Immunotherapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.|Immunology Program, Sloan-Kettering Institute, New York, New York 10065, USA.|Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D001438:Bacteroidaceae; D041963:Bacteroidetes / Q000235:genetics / Q000302:isolation & purification; D003092:Colitis / Q000139:chemically induced / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D011446:Prospective Studies; D012336:RNA, Ribosomal, 16S / Q000235:genetics*; D012307:Risk Factors; D017423:Sequence Analysis, RNA; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D000074324:Ipilimumab; D012336:RNA, Ribosomal, 16S
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