Epigenetic reprogramming of T cells: unlocking new avenues for cancer immunotherapy.

IF 7.7 2区医学 Q1 ONCOLOGY

Cancer and Metastasis Reviews Pub Date : 2024-03-01 Epub Date: 2024-01-18 DOI:10.1007/s10555-024-10167-w

Vipin Singh, Sandhik Nandi, Aritra Ghosh, Santanu Adhikary, Shravanti Mukherjee, Siddhartha Roy, Chandrima Das

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Abstract

T cells, a key component of cancer immunotherapy, undergo a variety of histone modifications and DNA methylation changes since their bone marrow progenitor stages before developing into CD8⁺ and CD4⁺ T cells. These T cell types can be categorized into distinct subtypes based on their functionality and properties, such as cytotoxic T cells (Tc), helper T cells (Th), and regulatory T cells (Treg) as subtypes for CD8⁺ and CD4⁺ T cells. Among these, the CD4⁺ CD25⁺ Tregs potentially contribute to cancer development and progression by lowering T effector (Teff) cell activity under the influence of the tumor microenvironment (TME). This contributes to the development of therapeutic resistance in patients with cancer. Subsequently, these individuals become resistant to monoclonal antibody therapy as well as clinically established immunotherapies. In this review, we delineate the different epigenetic mechanisms in cancer immune response and its involvement in therapeutic resistance. Furthermore, the possibility of epi-immunotherapeutic methods based on histone deacetylase inhibitors and histone methyltransferase inhibitors are under investigation. In this review we highlight EZH2 as the principal driver of cancer cell immunoediting and an immune escape regulator. We have addressed in detail how understanding T cell epigenetic regulation might bring unique inventive strategies to overcome drug resistance and increase the efficacy of cancer immunotherapy.

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T 细胞表观遗传学重编程：开启癌症免疫疗法的新途径。

T 细胞是癌症免疫疗法的关键组成部分，在发育成 CD8+ 和 CD4+ T 细胞之前，它们从骨髓原代阶段开始就经历了各种组蛋白修饰和 DNA 甲基化变化。这些 T 细胞类型可根据其功能和特性分为不同的亚型，如细胞毒性 T 细胞（Tc）、辅助性 T 细胞（Th）和调节性 T 细胞（Treg）是 CD8+ 和 CD4+ T 细胞的亚型。其中，CD4+ CD25+ Tregs 在肿瘤微环境（TME）的影响下降低了 T 效应细胞（Teff）的活性，从而可能导致癌症的发展和恶化。这有助于癌症患者产生抗药性。随后，这些患者会对单克隆抗体疗法和临床确立的免疫疗法产生耐药性。在这篇综述中，我们阐述了癌症免疫反应中不同的表观遗传机制及其在治疗耐药性中的参与作用。此外，基于组蛋白去乙酰化酶抑制剂和组蛋白甲基转移酶抑制剂的表观免疫治疗方法的可能性也在研究之中。在这篇综述中，我们强调 EZH2 是癌细胞免疫编辑的主要驱动因素和免疫逃逸调节器。我们详细探讨了了解 T 细胞表观遗传调控如何为克服耐药性和提高癌症免疫疗法疗效带来独特的创新策略。

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

Cancer and Metastasis Reviews 医学-肿瘤学

CiteScore

17.00

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Contemporary biomedical research is on the threshold of an era in which physiological and pathological processes can be analyzed in increasingly precise and mechanistic terms.The transformation of biology from a largely descriptive, phenomenological discipline to one in which the regulatory principles can be understood and manipulated with predictability brings a new dimension to the study of cancer and the search for effective therapeutic modalities for this disease. Cancer and Metastasis Reviews provides a forum for critical review and discussion of these challenging developments. A major function of the journal is to review some of the more important and interesting recent developments in the biology and treatment of malignant disease, as well as to highlight new and promising directions, be they technological or conceptual. Contributors are encouraged to review their personal work and be speculative.