表观遗传学
表观基因组
肿瘤微环境
生物
表观遗传学
重编程
DNA甲基化
生发中心
癌症研究
滤泡性淋巴瘤
B细胞
遗传学
淋巴瘤
免疫学
细胞
基因
基因表达
肿瘤细胞
抗体
作者
Rada Amin,Mounia S. Braza
标识
DOI:10.1186/s13046-021-02234-9
摘要
Follicular lymphoma (FL) is a B-cell non-Hodgkin lymphoma of germinal center (GC) origin with a distinctive tumor microenvironment (TME) and a unique spectrum of mutations. Despite the important therapeutic advances, FL is still incurable. During B-cell development, the GC reaction is a complex multistep process in which epigenetic regulators dynamically induce or suppress transcriptional programs. In FL, epigenetic gene mutations perturb the regulation of these programs, changing GC B-cell function and skewing differentiation towards tumor cells and altering the microenvironment interactions. FL pathogenesis and malignant transformation are promoted by epigenetic reprogramming of GC B cells that alters the immunological synapse and niche. Despite the extensive characterization of FL epigenetic signature and TME, the functional consequences of epigenetic dysregulation on TME and niche plasticity need to be better characterized. In this review, first we describe the most frequent epigenomic alterations in FL (KMT2D, CREBBP and EZH2) that affect the immunological niche, and their potential consequences on the informational transfer between tumor B cells and their microenvironment. Then, we discuss the latest progress to harness epigenetic targets for inhibiting the FL microenvironment. Finally, we highlight unexplored research areas and outstanding questions that should be considered for a successful long-term treatment of FL.
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