CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Recent Advances of RNA m(6)A Modifications in Cancer Immunoediting and Immunotherapy.
Recent Advances of RNA m(6)A Modifications in Cancer Immunoediting and Immunotherapy.
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肿瘤免疫治疗通过免疫检查点抑制剂或过继细胞转移来调节针对肿瘤的免疫反应,已成为一种新颖且有前景的肿瘤治疗方法。然而,只有少数患者表现出持久的反应,而大多数患者对免疫治疗具有耐药性。免疫系统可以矛盾地限制和促进肿瘤的发生和进展。这个过程被称为癌症免疫编辑。对免疫治疗耐药的机制似乎是癌细胞经历免疫编辑以逃避免疫系统的识别和清除。RNA修饰,特别是N6-甲基腺苷(m6A)甲基化,已成为各种转录后基因调控过程的关键调节因子,如RNA输出、剪接、稳定性和降解,这些过程在包括免疫系统发育和癌症发病机制在内的各种生理和病理过程中发挥着未被充分认识的作用。
因此,更深入地了解RNA修饰影响癌症免疫编辑过程的机制,可以为免疫治疗耐药机制以及克服这种耐药的策略提供见解。在本章中,我们简要介绍癌症免疫编辑和免疫治疗的背景。
我们还回顾并讨论了RNA m6A修饰在微调先天性和适应性免疫反应以及调节肿瘤逃避免疫监视中的作用和机制。最后,我们总结了当前针对m6A调节因子的癌症免疫治疗策略。
Cancer immunotherapy, which modulates immune responses against tumors using immune-checkpoint inhibitors or adoptive cell transfer, has emerged as a novel and promising therapy for tumors.
However, only a minority of patients demonstrate durable responses, while the majority of patients are resistant to immunotherapy. The immune system can paradoxically constrain and promote tumor development and progression. This process is referred to as cancer immunoediting. The mechanisms of resistance to immunotherapy seem to be that cancer cells undergo immunoediting to evade recognition and elimination by the immune system.
RNA modifications, specifically N 6 -methyladenosine (m 6 A) methylation, have emerged as a key regulator of various post-transcriptional gene regulatory processes, such as RNA export, splicing, stability, and degradation, which play unappreciated roles in various physiological and pathological processes, including immune system development and cancer pathogenesis.
Therefore, a deeper understanding of the mechanisms by which RNA modifications impact the cancer immunoediting process can provide insight into the mechanisms of resistance to immunotherapies and the strategies that can be used to overcome such resistance. In this chapter, we briefly introduce the background of cancer immunoediting and immunotherapy.
We also review and discuss the roles and mechanisms of RNA m 6 A modifications in fine-tuning the innate and adaptive immune responses, as well as in regulating tumor escape from immunosurveillance.
Finally, we summarize the current strategies targeting m 6 A regulators for cancer immunotherapy.
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