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Nat Commun. 2016 Feb 2;7:10391. doi: 10.1038/ncomms10391.

Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis.

Author information

1
Infectious Diseases Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.
2
Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
3
Weill Cornell Graduate School of Medical Sciences of Cornell University, New York, New York 10065, USA.
4
Weill Cornell Medical College, New York, New York 10065, USA.
5
Melanoma and Immunotherapy Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
6
Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
7
Computational Biology Program, Sloan-Kettering Institute, New York, New York 10065, USA.
8
Genomics Core Laboratory, Sloan-Kettering Institute, New York, New York 10065, USA.
9
Microbial Systems and Communities, Genome Sequencing and Analysis Program, The Broad Institute, Cambridge, Massachusetts 02142, USA.
10
Immunology Program, Sloan-Kettering Institute, New York, New York 10065, USA.
11
Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.

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.

PMID:
26837003
PMCID:
PMC4740747
DOI:
10.1038/ncomms10391
[Indexed for MEDLINE]
Free PMC Article

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