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

Nature Communications
Krista DubinJedd D Wolchok

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.

References

Dec 1, 1976·The American Journal of Clinical Nutrition·J J Ellestad-SayedE H Soule
Sep 1, 1968·The British Journal of Nutrition·M E CoatesG F Harrison
Sep 1, 1993·Digestive Diseases and Sciences·F KurokiM Fujishima
Mar 1, 1997·European Journal of Cancer Prevention : the Official Journal of the European Cancer Prevention Organisation (ECP)·M J Hill
Oct 8, 1999·European Journal of Gastroenterology & Hepatology·G RicciV Alvisi
Jun 3, 2006·Science·Steven R GillKaren E Nelson
Oct 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Harry SokolPhilippe Langella
Jun 10, 2009·Digestive Diseases and Sciences·James D LordGeorge B McDonald
Nov 3, 2009·Nucleic Acids Research·Minoru KanehisaMika Hirakawa
Jun 8, 2010·The New England Journal of Medicine·F Stephen HodiWalter J Urba
Jun 23, 2010·Proceedings of the National Academy of Sciences of the United States of America·June L Round, Sarkis K Mazmanian
Jun 28, 2011·Bioinformatics·Robert C EdgarRob Knight
Jun 28, 2011·Genome Biology·Nicola SegataCurtis Huttenhower
Jun 13, 2012·Nature Methods·Nicola SegataCurtis Huttenhower
Jun 16, 2012·Nature·UNKNOWN Human Microbiome Project Consortium
Jun 22, 2012·PLoS Computational Biology·Sahar AbubuckerCurtis Huttenhower
Oct 12, 2012·Nature·Lars Kjer-NielsenJames McCluskey
Feb 9, 2013·Science·Sebastian E WinterAndreas J Bäumler
Jan 24, 2014·Clinical and Experimental Immunology·N-E SerriariE Treiner
Jan 24, 2014·Science Translational Medicine·Jeremiah J FaithJeffrey I Gordon
Mar 5, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Suzanne L TopalianF Stephen Hodi
Apr 1, 2014·Cell·Yasmine Belkaid, Timothy W Hand
Jan 13, 2015·Annual Review of Immunology·Silvia Caballero, Eric G Pamer
Jun 17, 2015·Alimentary Pharmacology & Therapeutics·A GuptaS Khanna
Nov 7, 2015·Science·Marie VétizouLaurence Zitvogel

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Next ❯

Citations

Feb 16, 2016·Nature Reviews. Immunology·Yvonne Bordon
Nov 3, 2016·The New England Journal of Medicine·Douglas B JohnsonJavid J Moslehi
Oct 25, 2016·Chemical Research in Toxicology·Tiffany Cho, Jack Uetrecht
Mar 9, 2017·Nature Reviews. Gastroenterology & Hepatology·James L AlexanderJames M Kinross
Feb 2, 2017·Annual Review of Immunology·Amiran DzutsevGiorgio Trinchieri
May 19, 2016·Immunity·Margaret K CallahanJedd D Wolchok
Apr 20, 2017·Der Pathologe·V H KoelzerK D Mertz
May 23, 2017·Nature Reviews. Microbiology·Laurence ZitvogelGuido Kroemer
Apr 4, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·N ChaputF Carbonnel
Feb 9, 2017·Nature Medicine
Feb 19, 2017·La Revue de médecine interne·M KostineC Stavris
Feb 22, 2017·Microbial Pathogenesis·Jing-Zhang WangZhi-Jun Liu
Jan 27, 2017·Current Gastroenterology Reports·Peyton Cramer, Robert S Bresalier
Jan 14, 2017·Arthritis & Rheumatology·Maria E Suarez-AlmazorAdi Diab
Dec 23, 2016·Médecine sciences : M/S·Marie VétizouLaurence Zitvogel
Jan 20, 2017·Nature·Daniel S Chen, Ira Mellman
Jan 18, 2017·Seminars in Immunopathology·Franck CarbonnelCaroline Robert
Jun 18, 2017·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Leisha A EmensFrancesco M Marincola
Jul 7, 2017·Biologie aujourd'hui·Marie VétizouLaurence Zitvogel
May 10, 2017·CA: a Cancer Journal for Clinicians·Aadra P BhattScott J Bultman
Mar 8, 2018·Nature Reviews. Gastroenterology & Hepatology·Mark A SamaanPeter M Irving
Feb 15, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Julie R BrahmerUNKNOWN National Comprehensive Cancer Network
Mar 28, 2018·Journal of Hematology & Oncology·Ming YiKongming Wu
Apr 3, 2018·Journal of Translational Medicine·Michael F GowenIman Osman
Mar 2, 2018·Human Vaccines & Immunotherapeutics·Audrey Humphries, Adil Daud
Apr 5, 2018·Annals of Oncology : Official Journal of the European Society for Medical Oncology·L DerosaB Routy
Mar 17, 2018·Current Opinion in Supportive and Palliative Care·Hannah R WardillJoanne M Bowen
Oct 7, 2017·Current Opinion in Supportive and Palliative Care·Joanne M Bowen, Hannah R Wardill
Dec 7, 2017·Frontiers in Immunology·Kristian M Hargadon
Apr 11, 2018·Nature Reviews. Clinical Oncology·Bertrand RoutyGuido Kroemer
Jul 14, 2016·JPEN. Journal of Parenteral and Enteral Nutrition·Hannah G PiperAndrew Y Koh
Nov 7, 2017·Nature Reviews. Neurology·Lidia M YshiiRoland S Liblau
Feb 3, 2018·Immunology and Cell Biology·Jessica da Gama DuarteAndreas Behren
Jul 6, 2018·Cancer·Douglas B Johnson
Aug 6, 2018·Applied Microbiology and Biotechnology·Tiphaine C MartinMario Falchi
Aug 8, 2018·Proceedings of the National Academy of Sciences of the United States of America·Abhishek ShrivastavaHoward C Berg
Aug 30, 2018·International Journal of Cancer. Journal International Du Cancer·Kate R SecombeJoanne M Bowen
Oct 3, 2018·Expert Opinion on Drug Metabolism & Toxicology·Ramy K AzizMarwa T ElRakaiby
Aug 30, 2018·Current Opinion in Gastroenterology·Spyros I Siakavellas, Giorgos Bamias

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Datasets Mentioned

BETA
PRJNA302832

Methods Mentioned

BETA
PCR
PCRs

Software Mentioned

R Statistical Language
CTCAE
Silva
rpart
MetaPhlAn
R
HUMAnN
GraphPad Prism
LEfSe

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