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

Authors: Dubin, K.; Callahan, M. K.; Ren, B.; Khanin, R.; Viale, A.; Ling, L.; No, D.; Gobourne, A.; Littmann, E.; Huttenhower, C.; Pamer, E. G.; Wolchok, J. D.
Article 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. © 2016, Nature Publishing Group. All rights reserved.
Keywords: bacteroidetes phylum
Journal Title: Nature Communications
Volume: 7
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2016-02-02
Start Page: 10391
Language: English
DOI: 10.1038/ncomms10391
PROVIDER: scopus
PMCID: PMC4740747
PUBMED: 26837003
Notes: Article -- Export Date: 3 March 2016 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Jedd D Wolchok
    656 Wolchok
  2. Eric Pamer
    242 Pamer
  3. Margaret Kathleen Callahan
    102 Callahan
  4. Agnes Viale
    205 Viale
  5. Raya Khanin
    38 Khanin
  6. Daniel Christopher No
    5 No
  7. Lilan Ling
    38 Ling
  8. Krista Dubin
    4 Dubin