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
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 (, 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 ( 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
Keywords: Antibiotics
Immune checkpoint inhibitors
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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