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

Krista Dubin, Margaret K. Callahan, Boyu Ren, Raya Khanin, Agnes Viale, Lilan Ling, Daniel No, Asia Gobourne, Eric Littmann, Curtis Huttenhower, Eric G. Pamer () and Jedd D. Wolchok ()
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Krista Dubin: Infectious Diseases Service, Memorial Sloan Kettering Cancer Center
Margaret K. Callahan: Weill Cornell Medical College
Boyu Ren: Harvard School of Public Health
Raya Khanin: Computational Biology Program, Sloan-Kettering Institute
Agnes Viale: Genomics Core Laboratory, Sloan-Kettering Institute
Lilan Ling: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center
Daniel No: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center
Asia Gobourne: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center
Eric Littmann: Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center
Curtis Huttenhower: Harvard School of Public Health
Eric G. Pamer: Infectious Diseases Service, Memorial Sloan Kettering Cancer Center
Jedd D. Wolchok: Weill Cornell Medical College

Nature Communications, 2016, vol. 7, issue 1, 1-8

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms10391

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