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The paradox of immune checkpoint inhibition re-activating tuberculosis

Ahmed, Mohamed; Tezera, Liku B; Elkington, Paul T; Leslie, Alasdair J; (2022) The paradox of immune checkpoint inhibition re-activating tuberculosis. European Respiratory Journal , 60 (5) , Article 2102512. 10.1183/13993003.02512-2021. Green open access

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Abstract

By attenuating T-cell activation, immune checkpoints (ICs) limit optimal anti-tumour responses and IC inhibition (ICI) has emerged as a new therapy for a broad range of cancers. T-cell responses are indispensable to tuberculosis (TB) immunity in humans. However, boosting T-cell immunity in cancer patients by blocking the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis can trigger re-activation of latent TB. This phenomenon appears to contradict the prevailing thought that enhancing T-cell immunity to Mycobacterium tuberculosis will improve immune control of this pathogen. In support of this anecdotal human data, several murine studies have shown that PD-1 deficiency leads to severe TB disease and rapid death. These observations warrant a serious reconsideration of what constitutes effective TB immunity and how ICs contribute to it. Through restraining T-cell responses, ICs are critical to preventing excessive tissue damage and maintaining a range of effector functions. Bolstering this notion, inhibitory receptors limit pathology in respiratory infections such as influenza, where loss of negative immune regulation resulted in progressive immunopathology. In this review, we analyse the mechanisms of ICs in general and their role in TB in particular. We conclude with a reflection on the emerging paradigm and avenues for future research.

Type: Article
Title: The paradox of immune checkpoint inhibition re-activating tuberculosis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1183/13993003.02512-2021
Publisher version: https://doi.org/10.1183/13993003.02512-2021
Language: English
Additional information: Copyright © The authors 2022. This version is distributed under the terms of the Creative Commons Attribution Licence 4.0.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10160265
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