Epigenetic regulators combined with tumour immunotherapy: current status and perspectives.

IF 4.8 2区 医学 Q1 GENETICS & HEREDITY
Huan Zhang, Yutong Pang, Ling Yi, Xiaojue Wang, Panjian Wei, Haichao Wang, Shuye Lin
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Abstract

Immunotherapy, particularly immune checkpoint inhibitor therapy, has demonstrated clinical benefits in solid tumours. Despite its satisfactory clinical efficacy, it still faces several issues, such as limited eligibility, low response rates and cytotoxicity. Cancer epigenetics implies that tumour cells exhibit unique phenotypes because of their unique characteristics, thus reprogramming of the epigenome holds promise for cancer therapy. Epigenetic regulation plays an important role in regulating gene expression during tumour development and maintenance. Epigenetic regulators induce cancer cell cycle arrest, apoptosis and differentiation of cancer cells, thereby exerting anti-tumour effects. Recent studies have revealed a significant correlation between epigenetic regulatory factors and immune checkpoint therapy. Epigenetics can modulate various aspects of the tumour immune microenvironment and immune response to enhance the sensitivity of immunotherapy, such as lowering the concentration required and mitigating cytotoxicity. This review primarily discusses DNA methyltransferase inhibitors, histone deacetylase inhibitors, enhancer of zeste homolog 2 inhibitors and lysine-specific demethylase 1 inhibitors, which are associated with transcriptional repression. This repression alters the expression of genes involved in the immune checkpoint, thereby enhancing the effectiveness of immunotherapy. We also discuss the potential and challenges of tumour immunotherapy and highlight its advantages, application challenges and clinical research on integrating epigenetic regulatory factors with tumour immunotherapy.

表观遗传调控因子联合肿瘤免疫治疗:现状与展望。
免疫疗法,特别是免疫检查点抑制剂疗法,已经证明在实体肿瘤中的临床益处。尽管其临床疗效令人满意,但仍面临一些问题,如资格有限,反应率低和细胞毒性。癌症表观遗传学表明,肿瘤细胞由于其独特的特征而表现出独特的表型,因此表观基因组的重编程为癌症治疗带来了希望。表观遗传调控在肿瘤发生和维持过程中调控基因表达起着重要作用。表观遗传调控因子诱导癌细胞周期阻滞、凋亡和分化,从而发挥抗肿瘤作用。最近的研究揭示了表观遗传调控因子与免疫检查点治疗之间的显著相关性。表观遗传学可以调节肿瘤免疫微环境和免疫反应的各个方面,以提高免疫治疗的敏感性,例如降低所需的浓度和减轻细胞毒性。本文主要讨论了与转录抑制相关的DNA甲基转移酶抑制剂、组蛋白去乙酰化酶抑制剂、zeste同源物增强子2抑制剂和赖氨酸特异性去甲基化酶1抑制剂。这种抑制改变了参与免疫检查点的基因的表达,从而增强了免疫治疗的有效性。我们还讨论了肿瘤免疫治疗的潜力和挑战,重点介绍了肿瘤免疫治疗的优势、应用挑战以及表观遗传调控因子与肿瘤免疫治疗结合的临床研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
自引率
5.30%
发文量
150
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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