Dying to Be Noticed: Epigenetic Regulation of Immunogenic Cell Death for Cancer Immunotherapy.
Dying to Be Noticed: Epigenetic Regulation of Immunogenic Cell Death for Cancer Immunotherapy.
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DOI：
10.3389/fimmu.2018.00654
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发表时间：
2018
影响因子：
7.3
通讯作者：
Gujar S
中科院分区：
文献类型：
--
作者：
Cruickshank B;Giacomantonio M;Marcato P;McFarland S;Pol J;Gujar S
免疫原性细胞死亡（ICD）在凋亡性癌细胞死亡期间激活免疫系统的先天性和适应性臂。关于癌症免疫治疗，ICD的过程增强了来自垂死癌细胞的佐剂性和抗原性，因此促进了临床所需的抗肿瘤免疫的发展。癌症ICD需要呈现免疫调节的各种“标志”，其包括钙网蛋白的细胞表面易位、I型干扰素的产生以及高迁移率族蛋白-1和ATP的释放，其通过它们的相容作用诱导针对癌细胞的免疫应答。有趣的是，最近研究表观遗传修饰药物作为抗癌治疗药物的报告已经确定了与ICD标志的几种联系。表观遗传修饰剂对细胞活力具有直接影响，并且似乎通过积极地破坏肿瘤微环境相关的免疫逃避并帮助发展抗肿瘤免疫应答而从根本上改变癌细胞的免疫原性。在这篇综述中，我们批判性地讨论了目前的证据，确定表观遗传修饰和ICD标志之间的直接联系，并提出了一个否则知之甚少的作用表观遗传药物作为ICD诱导剂。我们进一步讨论了潜在的治疗创新，旨在诱导ICD在表观遗传药物治疗，产生高度有效的癌症免疫疗法。
Immunogenic cell death (ICD) activates both innate and adaptive arms of the immune system during apoptotic cancer cell death. With respect to cancer immunotherapy, the process of ICD elicits enhanced adjuvanticity and antigenicity from dying cancer cells and consequently, promotes the development of clinically desired antitumor immunity. Cancer ICD requires the presentation of various “hallmarks” of immunomodulation, which include the cell-surface translocation of calreticulin, production of type I interferons, and release of high-mobility group box-1 and ATP, which through their compatible actions induce an immune response against cancer cells. Interestingly, recent reports investigating the use of epigenetic modifying drugs as anticancer therapeutics have identified several connections to ICD hallmarks. Epigenetic modifiers have a direct effect on cell viability and appear to fundamentally change the immunogenic properties of cancer cells, by actively subverting tumor microenvironment-associated immunoevasion and aiding in the development of an antitumor immune response. In this review, we critically discuss the current evidence that identifies direct links between epigenetic modifications and ICD hallmarks, and put forward an otherwise poorly understood role for epigenetic drugs as ICD inducers. We further discuss potential therapeutic innovations that aim to induce ICD during epigenetic drug therapy, generating highly efficacious cancer immunotherapies.