Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-02-02

AUTHORS

Krista Dubin, Margaret K. Callahan, Boyu Ren, Raya Khanin, Agnes Viale, Lilan Ling, Daniel No, Asia Gobourne, Eric Littmann, Curtis Huttenhower, Eric G. Pamer, Jedd D. Wolchok

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. More... »

PAGES

10391

Journal

TITLE

Nature Communications

ISSUE

1

VOLUME

7

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms10391

DOI

http://dx.doi.org/10.1038/ncomms10391

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1037507717

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/26837003


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32 schema: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.
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39 Bacteroidetes phylum
40 Intestinal microbiome analysis
41 analysis
42 antibodies
43 bacteria
44 biomarkers
45 biosynthesis
46 cancer immunotherapy
47 checkpoint
48 colitis
49 colitis development
50 complications
51 composition
52 detectable inflammation
53 development
54 disease
55 disorders
56 fecal microbiota
57 genetic pathways
58 identification
59 immune-mediated colitis
60 immunologic checkpoints
61 immunotherapy
62 inflammation
63 inflammatory complications
64 inflammatory diseases
65 inflammatory disorders
66 intervention
67 intestinal microbiota
68 ipilimumab
69 ipilimumab treatment
70 melanoma
71 melanoma patients
72 members
73 metastatic melanoma
74 microbial members
75 microbiome analysis
76 microbiome composition
77 microbiota
78 microbiota composition
79 monoclonal antibodies
80 pathway
81 patients
82 paucity
83 phyla
84 polyamine transport
85 prospective study
86 representation
87 representation of bacteria
88 resistance
89 risk
90 risk of colitis
91 signaling
92 study
93 transport
94 treatment
95 vitamin biosynthesis
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