Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab

Study information

Reviewed Marked as Reviewed by Fatima on 2022/08/24

study design

prospective cohort

Citation

PMID PubMed identifier for scientific articles.

28368458

DOI Digital object identifier for electronic documents.

10.1093/annonc/mdx108

URI

https://pubmed.ncbi.nlm.nih.gov/28368458/

Authors

Chaput N, Lepage P, Coutzac C, Soularue E, Le Roux K, Monot C, Boselli L, Routier E, Cassard L, Collins M, Vaysse T, Marthey L, Eggermont A, Asvatourian V, Lanoy E, Mateus C, Robert C, Carbonnel F

Journal

Annals of oncology : official journal of the European Society for Medical Oncology

Year

2017

Keywords:

colitis, ipilimumab, melanoma, microbiota

BACKGROUND: Ipilimumab, an immune checkpoint inhibitor targeting CTLA-4, prolongs survival in a subset of patients with metastatic melanoma (MM) but can induce immune-related adverse events, including enterocolitis. We hypothesized that baseline gut microbiota could predict ipilimumab anti-tumor response and/or intestinal toxicity. PATIENTS AND METHODS: Twenty-six patients with MM treated with ipilimumab were prospectively enrolled. Fecal microbiota composition was assessed using 16S rRNA gene sequencing at baseline and before each ipilimumab infusion. Patients were further clustered based on microbiota patterns. Peripheral blood lymphocytes immunophenotypes were studied in parallel. RESULTS: A distinct baseline gut microbiota composition was associated with both clinical response and colitis. Compared with patients whose baseline microbiota was driven by Bacteroides (cluster B, n = 10), patients whose baseline microbiota was enriched with Faecalibacterium genus and other Firmicutes (cluster A, n = 12) had longer progression-free survival (P = 0.0039) and overall survival (P = 0.051). Most of the baseline colitis-associated phylotypes were related to Firmicutes (e.g. relatives of Faecalibacterium prausnitzii and Gemmiger formicilis), whereas no colitis-related phylotypes were assigned to Bacteroidetes. A low proportion of peripheral blood regulatory T cells was associated with cluster A, long-term clinical benefit and colitis. Ipilimumab led to a higher inducible T-cell COStimulator induction on CD4+ T cells and to a higher increase in serum CD25 in patients who belonged to Faecalibacterium-driven cluster A. CONCLUSION: Baseline gut microbiota enriched with Faecalibacterium and other Firmicutes is associated with beneficial clinical response to ipilimumab and more frequent occurrence of ipilimumab-induced colitis.

Experiment 1

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Reviewed Marked as Reviewed by Fatima on 2022/08/24

Curated date: 2022/07/14

Curator: Sharmilac

Revision editor(s): WikiWorks, Fatima, Sharmilac, Victoria

Subjects

Location of subjects: France

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Response to immunochemotherapy Response to immunochemotherapy,response to immunochemotherapy

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Resistance, Non responders, No colitis

Group 1 name Corresponds to the case (exposed) group for case-control studies: Responders, Colitis

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: MM patients that developed an immune-mediated colitis following ipilimumab treatment

Group 0 sample size Number of subjects in the control (unexposed) group: 19

Group 1 sample size Number of subjects in the case (exposed) group: 7

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: LEfSe

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.05

LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool: 3.5

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: decreased

Signature 1

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Reviewed Marked as Reviewed by Fatima on 2022/08/24

Curated date: 2022/08/24

Curator: Fatima

Revision editor(s): Fatima

Source: Figure 4

Description: Gut microbiota composition at baseline predicts ipilimumab-induced colitis.

Abundance in Group 1: increased abundance in Responders, Colitis

NCBI	Quality Control	Links
Bacteroides ovatus
Blautia obeum
Clostridiales bacterium
Fusicatenibacter saccharivorans
Gemmiger formicilis
Lachnospiraceae
Oscillospiraceae
Roseburia inulinivorans