Zhang Ruo-Nan, Jing Zhi-Qian, Zhang Lu, Sun Zhi-Jun
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Wuhan University, China.
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Wuhan University, China.
Cancer Lett. 2023 Oct 28;575:216413. doi: 10.1016/j.canlet.2023.216413. Epub 2023 Sep 26.
Immune checkpoint blockade therapy has revolutionized the field of cancer treatment, leading to durable responses in patients with advanced and metastatic cancers where conventional therapies were insufficient. However, factors like immunosuppressive cells and immune checkpoint molecules within the tumor microenvironment (TME) can suppress the immune system and thus negatively affect the efficiency of immune checkpoint inhibitors. Pyroptosis, a gasdermin-induced programmed cell death, could transform "cold tumors" to "hot tumors" to improve the milieu of TME, thus enhancing the immune response and preventing tumor growth. Recently, evidence showed that epigenetics could regulate pyroptosis, which further affects tumorigenesis, suggesting that epigenetics-based tumor cells pyroptosis could be a promising therapeutic strategy. Hence, this review focuses on the pyroptotic mechanism and summarizes three common types of epigenetics, DNA methylation, histone modification, and non-coding RNA, all of which have a role in regulating the expression of transcription factors and proteins involved in pyroptosis in cancer. Especially, we discuss targeting strategies on epigenetic-regulated pyroptosis and provide insights on the future trend of cancer research which may fuel cancer therapies into a new step.
免疫检查点阻断疗法彻底改变了癌症治疗领域，使晚期和转移性癌症患者在传统疗法效果不佳时能产生持久反应。然而，肿瘤微环境（TME）中的免疫抑制细胞和免疫检查点分子等因素会抑制免疫系统，从而对免疫检查点抑制剂的疗效产生负面影响。焦亡是一种由gasdermin诱导的程序性细胞死亡，它可以将“冷肿瘤”转变为“热肿瘤”，改善TME环境，从而增强免疫反应并抑制肿瘤生长。最近，有证据表明表观遗传学可以调节焦亡，进而影响肿瘤发生，这表明基于表观遗传学的肿瘤细胞焦亡可能是一种有前景的治疗策略。因此，本综述聚焦于焦亡机制，总结了三种常见的表观遗传学类型，即DNA甲基化、组蛋白修饰和非编码RNA，它们在调节参与癌症焦亡的转录因子和蛋白质表达方面均发挥作用。特别是，我们讨论了针对表观遗传学调控焦亡的靶向策略，并对癌症研究的未来趋势提供见解，这可能推动癌症治疗进入新的阶段。
