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The paradox of immune checkpoint inhibition reactivating tuberculosis

The paradox of immune checkpoint inhibition reactivating tuberculosis
The paradox of immune checkpoint inhibition reactivating tuberculosis
By attenuating T cell activation, immune checkpoints (ICs) limit optimal anti-tumor responses, and immune checkpoint inhibition (ICI), has emerged as a highly effective new therapy for a broad range of cancers. However, boosting T cell immunity in cancer patients by blocking the PD-1/PDL-1 axis can trigger reactivation of latent tuberculosis (TB). This phenomenon appears to contradict the prevailing thought that enhancing T cell immunity to Mycobacterium tuberculosis (Mtb) 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. Through restraining T cell responses, ICs are critical to preventing excessive tissue damage and maintaining a range of effector functions. Supporting 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 analyze 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.
0903-1936
Ahmed, Mohammed
fc39eac8-9145-4472-98a0-91ee866ef013
Tezera, Liku B.
e64520b0-6de3-4d53-9a35-67954fb876bc
Elkington, Paul
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Leslie, Alasdair
84d4f578-f3c0-46cc-9c83-a8d9bb40c38c
Ahmed, Mohammed
fc39eac8-9145-4472-98a0-91ee866ef013
Tezera, Liku B.
e64520b0-6de3-4d53-9a35-67954fb876bc
Elkington, Paul
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Leslie, Alasdair
84d4f578-f3c0-46cc-9c83-a8d9bb40c38c

Ahmed, Mohammed, Tezera, Liku B., Elkington, Paul and Leslie, Alasdair (2022) The paradox of immune checkpoint inhibition reactivating tuberculosis. European Respiratory Journal.

Record type: Review

Abstract

By attenuating T cell activation, immune checkpoints (ICs) limit optimal anti-tumor responses, and immune checkpoint inhibition (ICI), has emerged as a highly effective new therapy for a broad range of cancers. However, boosting T cell immunity in cancer patients by blocking the PD-1/PDL-1 axis can trigger reactivation of latent tuberculosis (TB). This phenomenon appears to contradict the prevailing thought that enhancing T cell immunity to Mycobacterium tuberculosis (Mtb) 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. Through restraining T cell responses, ICs are critical to preventing excessive tissue damage and maintaining a range of effector functions. Supporting 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 analyze 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.

Text
ERJ-02512-2021_Author_accepted
Restricted to Repository staff only until 18 April 2023.
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Published date: 18 April 2022

Identifiers

Local EPrints ID: 456896
URI: http://eprints.soton.ac.uk/id/eprint/456896
ISSN: 0903-1936
PURE UUID: 613c8121-ab95-4107-b58f-856706f7b931
ORCID for Paul Elkington: ORCID iD orcid.org/0000-0003-0390-0613

Catalogue record

Date deposited: 16 May 2022 16:39
Last modified: 24 Jul 2022 01:44

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Contributors

Author: Mohammed Ahmed
Author: Liku B. Tezera
Author: Paul Elkington ORCID iD
Author: Alasdair Leslie

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