Ehrlich Marcelo, Bacharach Eran
Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
Cancers (Basel). 2021 Feb 24;13(5):939. doi: 10.3390/cancers13050939.
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.
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、重编程细胞代谢、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。这种编辑过程包括细胞自主免疫基因表达和/或功能的降低，使得肿瘤能够逃避免疫，同时削弱抗病毒防御。结合癌细胞代谢中癌基因增强的合成代谢特性，抗病毒防御的这种减弱有助于病毒复制以及溶瘤病毒（OVs）对恶性细胞的选择性。在此，我们综述癌基因介导的转化和肿瘤免疫编辑如何结合起来改变肿瘤细胞的细胞内环境，以利于OV复制。我们还探讨致癌信号与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。综合来看，呈现出的图景是，OVs和表观遗传修饰剂是一个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。
