Oncolytic Virotherapy: The Cancer Cell Side.
Oncolytic Virotherapy: The Cancer Cell Side.
复制标题
DOI：
10.3390/cancers13050939
复制
发表时间：
2021-02-24
期刊：
影响因子：
5.2
通讯作者：
Bacharach E
中科院分区：
文献类型：
--
作者：
Ehrlich M;Bacharach E
溶瘤病毒（OV）是一种有前途的免疫疗法，可以特异性靶向并杀死癌细胞并刺激抗肿瘤免疫。而不同的OV被赋予了不同的特征，增强了它们对肿瘤细胞的特异性；癌细胞的属性也对这种特异性做出了重要贡献。这些特征包括先天免疫缺陷，包括抗病毒反应和恶性细胞的代谢重编程。支持 OV 复制的致瘤特征可能是转化过程所固有的（例如，给定癌基因活性的直接结果），或者是在肿瘤免疫编辑（抗肿瘤免疫应用的选择过程）过程中获得的。癌基因诱导的表观遗传沉默在癌细胞免疫刺激抗病毒反应的负调节中发挥重要作用。这种沉默的逆转还可以通过激活内源性逆转录因子以病毒模拟的形式提供强免疫刺激剂。在这里，我们回顾了支持病毒复制、肿瘤免疫编辑的癌细胞特征，以及致癌信号、DNA 甲基化和病毒溶瘤之间的联系。因此，本综述集中于恶性细胞，而不同 OV 的详细描述可以在本期的随附评论中找到。细胞自主免疫基因介导抗病毒防御的多个阶段，包括识别入侵病原体、抑制病毒复制、细胞代谢重编程、程序性细胞死亡、旁分泌诱导抗病毒状态以及激活免疫刺激性炎症。在肿瘤发展和/或免疫治疗环境中，免疫系统施加的选择性压力导致肿瘤免疫编辑，即癌细胞免疫刺激潜力的降低。这种编辑过程包括减少细胞自主免疫基因的表达和/或功能，从而允许肿瘤逃避免疫，同时削弱抗病毒防御。与癌基因增强的癌细胞代谢合成代谢性质相结合，抗病毒防御的减弱有助于病毒复制和溶瘤病毒（OV）对恶性细胞的选择性。在这里，我们回顾了癌基因介导的转化和肿瘤免疫编辑结合改变肿瘤细胞的细胞内环境以有利于 OV 复制的方式。我们还探索了致癌信号和表观遗传沉默之间的功能联系，以及限制这种沉默导致免疫激活的方式。总而言之，OV 和表观遗传修饰剂是不断发展的治疗工具箱的一部分，该工具箱利用激活抗肿瘤免疫来进行癌症治疗。
Oncolytic viruses (OVs) are a promising immunotherapy that specifically target and kill cancer cells and stimulate anti-tumor immunity. While different OVs are endowed with distinct features, which enhance their specificity towards tumor cells; attributes of the cancer cell also critically contribute to this specificity. Such features comprise defects in innate immunity, including antiviral responses, and the metabolic reprogramming of the malignant cell. The tumorigenic features which support OV replication can be intrinsic to the transformation process (e.g., a direct consequence of the activity of a given oncogene), or acquired in the course of tumor immunoediting—the selection process applied by antitumor immunity. Oncogene-induced epigenetic silencing plays an important role in negative regulation of immunostimulatory antiviral responses in the cancer cells. Reversal of such silencing may also provide a strong immunostimulant in the form of viral mimicry by activation of endogenous retroelements. Here we review features of the cancer cell that support viral replication, tumor immunoediting and the connection between oncogenic signaling, DNA methylation and viral oncolysis. As such, this review concentrates on the malignant cell, while detailed description of different OVs can be found in the accompanied reviews of this issue. Cell autonomous immunity genes mediate the multiple stages of anti-viral defenses, including recognition of invading pathogens, inhibition of viral replication, reprogramming of cellular metabolism, programmed-cell-death, paracrine induction of antiviral state, and activation of immunostimulatory inflammation. In tumor development and/or immunotherapy settings, selective pressure applied by the immune system results in tumor immunoediting, a reduction in the immunostimulatory potential of the cancer cell. This editing process comprises the reduced expression and/or function of cell autonomous immunity genes, allowing for immune-evasion of the tumor while concomitantly attenuating anti-viral defenses. Combined with the oncogene-enhanced anabolic nature of cancer-cell metabolism, this attenuation of antiviral defenses contributes to viral replication and to the selectivity of oncolytic viruses (OVs) towards malignant cells. Here, we review the manners by which oncogene-mediated transformation and tumor immunoediting combine to alter the intracellular milieu of tumor cells, for the benefit of OV replication. We also explore the functional connection between oncogenic signaling and epigenetic silencing, and the way by which restriction of such silencing results in immune activation. Together, the picture that emerges is one in which OVs and epigenetic modifiers are part of a growing therapeutic toolbox that employs activation of anti-tumor immunity for cancer therapy.
登录
查看更多内容
影响因子：
11.1
作者：
Bhattacharya, Sabyasachi;Katlinski, Kanstantsin V.;Reichert, Maximilian;Takano, Shigetsugu;Brice, Angela;Zhao, Bin;Yu, Qiujing;Zheng, Hui;Carbone, Christopher J.;Katlinskaya, Yuliya V.;Leu, N. Adrian;McCorkell, Kelly A.;Srinivasan, Satish;Girondo, Melanie;Rui, Hallgeir;May, Michael J.;Avadhani, Narayan G.;Rustgi, Anil K.;Fuchs, Serge Y.
通讯作者：
Fuchs, Serge Y.
影响因子：
11.2
作者：
Dunn, GP;Sheehan, KCF;Schreiber, RD
通讯作者：
Schreiber, RD
影响因子：
5.4
作者：
Budt, Matthias;Niederstadt, Lars;Brune, Wolfram
通讯作者：
Brune, Wolfram
影响因子：
3.7
作者：
Nobeyama Y;Nakagawa H
通讯作者：
Nakagawa H
影响因子：
5.4
作者：
Christian, Sherri L.;Collier, Thaddeus W.;Hirasawa, Kensuke
通讯作者：
Hirasawa, Kensuke