T-cell dysfunction in chronic lymphocytic leukemia from an epigenetic perspective.
Haematologica
; 106(5): 1234-1243, 2021 05 01.
Article
em En
| MEDLINE
| ID: mdl-33691381
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leucemia Linfocítica Crônica de Células B
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Haematologica
Ano de publicação:
2021
Tipo de documento:
Article