PD-1/PD-L1 axis regulation in cancer therapy: The role of long non-coding RNAs and microRNAs
PD-1/PD-L1 axis regulation in cancer therapy: The role of long non-coding RNAs and microRNAs
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DOI：
10.1016/j.lfs.2020.117899
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发表时间：
2020-09-01
期刊：
影响因子：
6.1
通讯作者：
Najafi, Masoud
中科院分区：
文献类型：
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作者：
Ashrafizadeh, Milad;Zarrabi, Ali;Najafi, Masoud
肿瘤免疫治疗是当今一个发展迅速的领域。在不同的分子通路中，PD-1/PD-L1信号通路在免疫应答的调节中起着重要的作用。已有研究表明，PD-1/PD-L1轴的激活与T细胞耗竭、T细胞凋亡及T细胞增殖能力下降有关。PD-1/PD-L1轴为癌细胞的免疫逃逸提供了条件，并干扰了抗肿瘤免疫。靶向PD-1/PD-L1轴在肿瘤免疫治疗中的作用已引起人们的广泛关注。发现这一轴的上游调控因子似乎可以拓宽我们的认识，为肿瘤免疫治疗开发新型抗肿瘤药物。微小RNAs(MiRs)和长非编码RNAs(LncRNAs)是非编码RNAs的关键亚类，因为它们可以通过靶向不同的分子途径来调节各种生物过程。在这篇综述中，我们证明了抑癌基因miRs和lncRNAs通过抑制PD-1/PD-L1轴提供抗肿瘤免疫，从而可能成为其他分子途径如STAT、ZeB、PI3K/Akt等的靶点。相反，癌基因miRs和lncRNAs诱导PD-1/PD-L1轴。识别miR/PD-1和LncRNA/PD-1信号通路有助于我们寻找有效的肿瘤免疫治疗药物，并可以指导我们对上述信号通路的基因操作。
Cancer immunotherapy is a growing field nowadays. Among different molecular pathways, PD-1/PD-L1 signaling pathway plays a significant role in the regulation of immune responses. It has been reported that stimulation of PD-1/PD-L1 axis is correlated with T cell exhaustion, T cell apoptosis, and their reduced capability in proliferation. PD-1/PD-L1 axis provides a condition for immune evasion of cancer cells and interferes with antitumor immunity. Much attention has been directed towards targeting PD-1/PD-L1 axis in cancer immunotherapy. It seems that identification of upstream modulators of this axis can broaden our understanding to develop novel anti-tumor drugs for cancer immunotherapy. MicroRNAs (miRs) and long non-coding RNAs (lncRNAs) are key subcategories of non-coding RNAs, since they can regulate various biological processes by targeting different molecular pathways. In this review, we demonstrate that onco-suppressor miRs and lncRNAs inhibit PD-1/PD-L1 axis to provide anti-tumor immunity and in this way, other molecular pathways such as STAT, ZEB, PI3K/Akt and so on may be targeted. In contrast, oncogene miRs and lncRNAs induce PD-1/PD-L1 axis. Identification of miR/PD-1 and lncRNA/PD-1 signaling pathways can help us in finding an effective drug for cancer immunotherapy, and can direct us towards genetic manipulation of the aforementioned pathways.