Huang Jau-Ling, Chen Si-Yun, Lin Chang-Shen
Department of Bioscience Technology, College of Health Science, Chang Jung Christian University, Tainan 711, Taiwan.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
J Pers Med. 2022 Apr 1;12(4):556. doi: 10.3390/jpm12040556.
Cancer stem cells (CSCs) are a small subset of cancer cells and are thought to play a critical role in the initiation and maintenance of tumor mass. CSCs exhibit similar hallmarks to normal stem cells, such as self-renewal, differentiation, and homeostasis. In addition, CSCs are equipped with several features so as to evade anticancer mechanisms. Therefore, it is hard to eliminate CSCs by conventional anticancer therapeutics that are effective at clearing bulk cancer cells. Interferons are innate cytokines and are the key players in immune surveillance to respond to invaded pathogens. Interferons are also crucial for adaptive immunity for the killing of specific aliens including cancer cells. However, CSCs usually evolve to escape from interferon-mediated immune surveillance and to shape the niche as a "cold" tumor microenvironment (TME). These CSC characteristics are related to their unique epigenetic regulations that are different from those of normal and bulk cancer cells. In this review, we introduce the roles of epigenetic modifiers, focusing on LSD1, BMI1, G9a, and SETDB1, in contributing to CSC characteristics and discussing the interplay between CSCs and interferon response. We also discuss the emerging strategy for eradicating CSCs by targeting these epigenetic modifiers, which can elevate cytosolic nuclei acids, trigger interferon response, and reshape a "hot" TME for improving cancer immunotherapy. The key epigenetic and immune genes involved in this crosstalk can be used as biomarkers for precision oncology.
癌症干细胞（CSCs）是癌细胞中的一小部分，被认为在肿瘤块的起始和维持中起关键作用。CSCs表现出与正常干细胞相似的特征，如自我更新、分化和内环境稳定。此外，CSCs具备多种特征以逃避抗癌机制。因此，通过有效清除大量癌细胞的传统抗癌疗法很难消除CSCs。干扰素是先天性细胞因子，是免疫监视中应对入侵病原体的关键参与者。干扰素对于包括癌细胞在内的特定外来物的杀伤所产生的适应性免疫也至关重要。然而，CSCs通常会进化以逃避干扰素介导的免疫监视，并将生态位塑造成“冷”肿瘤微环境（TME）。这些CSC特征与其独特的表观遗传调控有关，这些调控不同于正常细胞和大量癌细胞的表观遗传调控。在本综述中，我们介绍表观遗传修饰因子的作用，重点关注赖氨酸特异性去甲基化酶1（LSD1）、多梳蛋白抑制复合物2核心蛋白BMI1、组蛋白甲基转移酶G9a和组蛋白赖氨酸N-甲基转移酶SETDB1，它们对CSC特征的影响，并讨论CSCs与干扰素反应之间的相互作用。我们还讨论了通过靶向这些表观遗传修饰因子来根除CSCs的新兴策略，这可以提高胞质核酸水平、触发干扰素反应并重塑“热”TME以改善癌症免疫治疗。参与这种相互作用的关键表观遗传和免疫基因可作为精准肿瘤学的生物标志物。
