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Antibiotic therapy and outcome from immune-checkpoint inhibitors

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Title: Antibiotic therapy and outcome from immune-checkpoint inhibitors
Authors: Pinato, DJ
Gramenitskaya, D
Altmann, DM
Boyton, RJ
Mullish, BH
Marchesi, JR
Bower, M
Item Type: Journal Article
Abstract: Sensitivity to immune checkpoint inhibitor (ICPI) therapy is governed by a complex interplay of tumor and host-related determinants. Epidemiological studies have highlighted that exposure to antibiotic therapy influences the probability of response to ICPI and predict for shorter patient survival across malignancies. Whilst a number of studies have reproducibly documented the detrimental effect of broad-spectrum antibiotics, the immune-biologic mechanisms underlying the association with outcome are poorly understood. Perturbation of the gut microbiota, an increasingly well-characterized factor capable of influencing ICPI-mediated immune reconstitution, has been indicated as a putative mechanism to explain the adverse effects attributed to antibiotic exposure in the context of ICPI therapy. Prospective studies are required to validate antibiotic-mediated gut perturbations as a mechanism of ICPI refractoriness and guide the development of strategies to overcome this barrier to an effective delivery of anti-cancer immunotherapy.
Issue Date: 6-Nov-2019
Date of Acceptance: 5-Oct-2019
URI: http://hdl.handle.net/10044/1/73861
DOI: 10.1186/s40425-019-0775-x
ISSN: 2051-1426
Publisher: BioMed Central
Journal / Book Title: Journal for ImmunoTherapy of Cancer
Volume: 7
Issue: 1
Copyright Statement: © 2019 The Author(s). This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Sponsor/Funder: Medical Research Council
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Imperial College Healthcare NHS Trust- BRC Funding
Wellcome Trust
Funder's Grant Number: MR/R00875/1
MR/R000875/1
RDA02
RDBO1
204834/Z/16/Z
Keywords: Antibiotics
Immune checkpoint inhibitors
Survival
Publication Status: Published
Article Number: 287
Online Publication Date: 2019-11-06
Appears in Collections:Division of Surgery
Division of Cancer
Faculty of Medicine



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