Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis
By K. Dubin, M. Callahan, Boyu Ren, Raya Khanin, A. Viale, Lilan Ling, Daniel No, Asia Gobourne, E. Littmann, Curtis Huttenhower and 2 more. Nature Communications, 2016
915 citations recorded by the source corpus.
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. A subset of cancer patients treated with immune checkpoint blockade develops colitis. Here the authors show that lower abundance of Bacteroidetes and vitamin B biosynthetic modules in fecal samples of melanoma patients can predict their susceptibility to colitis following anti-CTLA-4 treatment.
Subfields: Dermatology, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/30974fec963f6877d64fc2196d7415a74aa38328
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Citations in the corpus
- The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy. (2018, methodology): “…in techniques used to analyze samples and reference databases used for analysis, which varied widely across the studies (Chaput et al., 2017; Dubin et al., 2016; Frankel et al., 2017; Gopalakrishnan et al., 2018; Jenq et al., 2015; Matson et al., 2018; Peled et al., 2017; Routy et al.,…”
- Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab (2017, background): “recently showed an increased representation of bacteria belonging to the Bacteroidetes phylum among patients who remain free of ipilimumab-induced colitis in an American cohort of 34 patients [31].”
- Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2018, background): “More specifically, at baseline, an increased presence of bacteria belonging to the Bacteroidetes phylum species was found in patients who remained free of colitis after ipilimumab treatment [46].”
- Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. (2017, background): “More specifically, at baseline, an increased presence of bacteria belonging to the Bacteroidetes phylum species was found in patients who remained free of colitis after ipilimumab treatment [45].”
- Antibiotic-Induced Changes in the Intestinal Microbiota and Disease. (2016, methodology): “Accordingly, a recent analysis of a cohort of patients undergoing ipilimumab treatment identified members of the Bacteroidetes phylum as being significantly increased in subjects who did not develop colitis [148].”