Department of Medical Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran 1417613151, Iran.
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mol Ther. 2021 Sep 1;29(9):2640-2659. doi: 10.1016/j.ymthe.2021.08.003. Epub 2021 Aug 6.
Chimeric antigen receptor (CAR) T cell therapy has led to a paradigm shift in cancer immunotherapy, but still several obstacles limit CAR T cell efficacy in cancers. Advances in high-throughput technologies revealed new insights into the role that epigenetic reprogramming plays in T cells. Mechanistic studies as well as comprehensive epigenome maps revealed an important role for epigenetic remodeling in T cell differentiation. These modifications shape the overall immune response through alterations in T cell phenotype and function. Here, we outline how epigenetic modifications in CAR T cells can overcome barriers limiting CAR T cell effectiveness, particularly in immunosuppressive tumor microenvironments. We also offer our perspective on how selected epigenetic modifications can boost CAR T cells to ultimately improve the efficacy of CAR T cell therapy.
嵌合抗原受体 (CAR) T 细胞疗法在癌症免疫疗法方面带来了范式转变，但仍有几个障碍限制了 CAR T 细胞在癌症中的疗效。高通量技术的进步揭示了表观遗传重编程在 T 细胞中的作用的新见解。机制研究和全面的表观基因组图谱揭示了表观遗传重塑在 T 细胞分化中的重要作用。这些修饰通过改变 T 细胞表型和功能来塑造整体免疫反应。在这里，我们概述了 CAR T 细胞中的表观遗传修饰如何克服限制 CAR T 细胞有效性的障碍，特别是在免疫抑制性肿瘤微环境中。我们还提供了我们的观点，即如何选择表观遗传修饰来增强 CAR T 细胞，最终提高 CAR T 细胞疗法的疗效。
