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

Author

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  • Krista Dubin

    (Infectious Diseases Service, Memorial Sloan Kettering Cancer Center
    Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center
    Weill Cornell Graduate School of Medical Sciences of Cornell University)

  • Margaret K. Callahan

    (Weill Cornell Medical College
    Melanoma and Immunotherapy Service, Memorial Sloan Kettering Cancer Center)

  • 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
    Microbial Systems and Communities, Genome Sequencing and Analysis Program, The Broad Institute)

  • Eric G. Pamer

    (Infectious Diseases Service, Memorial Sloan Kettering Cancer Center
    Lucille Castori Center for Microbes, Inflammation and Cancer, Memorial Sloan Kettering Cancer Center
    Immunology Program, Sloan-Kettering Institute)

  • Jedd D. Wolchok

    (Weill Cornell Medical College
    Melanoma and Immunotherapy Service, Memorial Sloan Kettering Cancer Center
    Immunology Program, Sloan-Kettering Institute
    Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center)

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.

Suggested Citation

  • Krista Dubin & Margaret K. Callahan & Boyu Ren & Raya Khanin & Agnes Viale & Lilan Ling & Daniel No & Asia Gobourne & Eric Littmann & Curtis Huttenhower & Eric G. Pamer & Jedd D. Wolchok, 2016. "Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis," Nature Communications, Nature, vol. 7(1), pages 1-8, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10391
    DOI: 10.1038/ncomms10391
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    Cited by:

    1. Jonathan W. Lo & Jan-Hendrik Schroeder & Luke B. Roberts & Rami Mohamed & Domenico Cozzetto & Gordon Beattie & Omer S. Omer & Ellen M. Ross & Frank Heuts & Geraldine M. Jowett & Emily Read & Matthew M, 2024. "CTLA-4 expressing innate lymphoid cells modulate mucosal homeostasis in a microbiota dependent manner," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Jonathan W. Lo & Domenico Cozzetto & James L. Alexander & Nathan P. Danckert & Matthew Madgwick & Naomi Knox & Jillian Yong Xin Sieh & Marton Olbei & Zhigang Liu & Hajir Ibraheim & Jesus Miguens Blanc, 2023. "Immune checkpoint inhibitor-induced colitis is mediated by polyfunctional lymphocytes and is dependent on an IL23/IFNγ axis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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