Cargando…

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 sign...

Descripción completa

Detalles Bibliográficos
Autores principales: Peters, Fleur S., Strefford, Jonathan C., Eldering, Eric, Kater, Arnon P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586819/
https://www.ncbi.nlm.nih.gov/pubmed/33691381
http://dx.doi.org/10.3324/haematol.2020.267914
_version_ 1784597966782201856
author Peters, Fleur S.
Strefford, Jonathan C.
Eldering, Eric
Kater, Arnon P.
author_facet Peters, Fleur S.
Strefford, Jonathan C.
Eldering, Eric
Kater, Arnon P.
author_sort Peters, Fleur S.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8586819
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Fondazione Ferrata Storti
record_format MEDLINE/PubMed
spelling pubmed-85868192021-11-24 T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective Peters, Fleur S. Strefford, Jonathan C. Eldering, Eric Kater, Arnon P. Haematologica Review Article 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. Fondazione Ferrata Storti 2021-03-11 /pmc/articles/PMC8586819/ /pubmed/33691381 http://dx.doi.org/10.3324/haematol.2020.267914 Text en Copyright© 2021 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Review Article
Peters, Fleur S.
Strefford, Jonathan C.
Eldering, Eric
Kater, Arnon P.
T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective
title T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective
title_full T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective
title_fullStr T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective
title_full_unstemmed T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective
title_short T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective
title_sort t-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8586819/
https://www.ncbi.nlm.nih.gov/pubmed/33691381
http://dx.doi.org/10.3324/haematol.2020.267914
work_keys_str_mv AT petersfleurs tcelldysfunctioninchroniclymphocyticleukemiafromanepigeneticperspective
AT streffordjonathanc tcelldysfunctioninchroniclymphocyticleukemiafromanepigeneticperspective
AT elderingeric tcelldysfunctioninchroniclymphocyticleukemiafromanepigeneticperspective
AT katerarnonp tcelldysfunctioninchroniclymphocyticleukemiafromanepigeneticperspective