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Antibiotic therapy and outcome from immune-checkpoint inhibitors

Pinato, David J., Gramenitskaya, Daria, Altmann, Daniel M., Boyton, Rosemary J., Mullish, Benjamin H., Marchesi, Julian R. and Bower, Mark 2019. Antibiotic therapy and outcome from immune-checkpoint inhibitors. Journal for ImmunoTherapy of Cancer 7 (1) , 287. 10.1186/s40425-019-0775-x

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
ISSN: 2051-1426
Date of First Compliant Deposit: 18 November 2019
Date of Acceptance: 9 October 2019
Last Modified: 19 Nov 2019 14:15
URI: http://orca.cf.ac.uk/id/eprint/126920

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