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

Nat Commun
Authors
Keywords
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.

Year of Publication
2016
Journal
Nat Commun
Volume
7
Pages
10391
Date Published
2016 Feb 02
ISSN
2041-1723
URL
DOI
10.1038/ncomms10391
PubMed ID
26837003
PubMed Central ID
PMC4740747
Links
Grant list
5T32GM007739 / GM / NIGMS NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
R01 AI42135 / AI / NIAID NIH HHS / United States
P30CA008748 / CA / NCI NIH HHS / United States
R01 AI042135 / AI / NIAID NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States