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T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective

T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective
T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective
Cellular immunotherapeutic approaches such as chimeric antigen receptor (CAR) T-cell therapy in chronic lymphocytic leukemia (CLL) thus far have not met the high expectations. Therefore it is essential to better understand the molecular mechanisms of CLLinduced T-cell dysfunction. Even though a significant number of studies are available on T-cell function and dysfunction in CLL patients, none examine dysfunction at the epigenomic level. In non-malignant T-cell research, epigenomics is widely employed to define the differentiation pathway into T-cell exhaustion. Additionally, metabolic restrictions in the tumor microenvironment that cause T-cell dysfunction are often mediated by epigenetic changes. With this review paper we argue that understanding the epigenetic (dys)regulation in T cells of CLL patients should be leveled to the knowledge we currently have of the neoplastic B cells themselves. This will permit a complete understanding of how these immune cell interactions regulate T- and B-cell function. Here we relate the cellular and phenotypic characteristics of CLL-induced T-cell dysfunction to epigenetic studies of T-cell regulation emerging from chronic viral infection and tumor models. This paper proposes a framework for future studies into the epigenetic regulation of CLL-induced Tcell dysfunction, knowledge that will help to guide improvements in the utility of autologous T-cell based therapies in CLL.
0390-6078
1234-1243
Peters, Fleur S.
303a2901-5f0d-4822-aa87-b0c882547e9e
Strefford, Jonathan
3782b392-f080-42bf-bdca-8aa5d6ca532f
Eldering, Eric
3ceb48b0-8d2c-47b6-b8a0-0aff486e2e0f
Kater, Arnon P.
b0c9bb11-e6e5-4c8f-be47-a0b63aca2073
Peters, Fleur S.
303a2901-5f0d-4822-aa87-b0c882547e9e
Strefford, Jonathan
3782b392-f080-42bf-bdca-8aa5d6ca532f
Eldering, Eric
3ceb48b0-8d2c-47b6-b8a0-0aff486e2e0f
Kater, Arnon P.
b0c9bb11-e6e5-4c8f-be47-a0b63aca2073

Peters, Fleur S., Strefford, Jonathan, Eldering, Eric and Kater, Arnon P. (2021) T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective. Haematologica, 106 (5), 1234-1243. (doi:10.3324/haematol.2020.267914).

Record type: Review

Abstract

Cellular immunotherapeutic approaches such as chimeric antigen receptor (CAR) T-cell therapy in chronic lymphocytic leukemia (CLL) thus far have not met the high expectations. Therefore it is essential to better understand the molecular mechanisms of CLLinduced T-cell dysfunction. Even though a significant number of studies are available on T-cell function and dysfunction in CLL patients, none examine dysfunction at the epigenomic level. In non-malignant T-cell research, epigenomics is widely employed to define the differentiation pathway into T-cell exhaustion. Additionally, metabolic restrictions in the tumor microenvironment that cause T-cell dysfunction are often mediated by epigenetic changes. With this review paper we argue that understanding the epigenetic (dys)regulation in T cells of CLL patients should be leveled to the knowledge we currently have of the neoplastic B cells themselves. This will permit a complete understanding of how these immune cell interactions regulate T- and B-cell function. Here we relate the cellular and phenotypic characteristics of CLL-induced T-cell dysfunction to epigenetic studies of T-cell regulation emerging from chronic viral infection and tumor models. This paper proposes a framework for future studies into the epigenetic regulation of CLL-induced Tcell dysfunction, knowledge that will help to guide improvements in the utility of autologous T-cell based therapies in CLL.

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Accepted/In Press date: 18 February 2021
e-pub ahead of print date: 11 March 2021
Published date: May 2021
Additional Information: Funding Information: JCS has previously received funding from Roche and currently receives funding from Bloodwise, the Kay Kendall Leukaemia Fund and Cancer Research UK; APK is funded by a Dutch Research Council (NWO) VIDI grant and an European Research Council (ERC) Consolidator grant; FSP and EE declare no conflicts of interest. Publisher Copyright: © 2021 Ferrata Storti Foundation

Identifiers

Local EPrints ID: 447720
URI: http://eprints.soton.ac.uk/id/eprint/447720
ISSN: 0390-6078
PURE UUID: 380e1256-05f7-41c7-bee1-18b5564f4e4e
ORCID for Jonathan Strefford: ORCID iD orcid.org/0000-0002-0972-2881

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Date deposited: 18 Mar 2021 17:55
Last modified: 17 Mar 2024 02:59

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Contributors

Author: Fleur S. Peters
Author: Eric Eldering
Author: Arnon P. Kater

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