Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, 34956 Istanbul, Turkey; Center of Excellence for Functional Surfaces and Interfaces (EFSUN), Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla, Istanbul 34956, Turkey.
Life Sci. 2020 Sep 1;256:117899. doi: 10.1016/j.lfs.2020.117899. Epub 2020 Jun 3.
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 anti-tumor 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.
癌症免疫疗法是当今一个不断发展的领域。在不同的分子途径中，PD-1/PD-L1 信号通路在免疫反应的调节中起着重要作用。据报道，PD-1/PD-L1 轴的刺激与 T 细胞耗竭、T 细胞凋亡及其增殖能力降低有关。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。人们对靶向 PD-1/PD-L1 轴的癌症免疫疗法给予了极大的关注。似乎识别该轴的上游调节剂可以拓宽我们的理解，从而开发用于癌症免疫疗法的新型抗肿瘤药物。微小 RNA（miRs）和长链非编码 RNA（lncRNAs）是非编码 RNA 的主要亚类，因为它们可以通过靶向不同的分子途径来调节各种生物学过程。在这篇综述中，我们证明了抑癌 miR 和 lncRNA 抑制 PD-1/PD-L1 轴以提供抗肿瘤免疫，从而可以靶向其他分子途径，如 STAT、ZEB、PI3K/Akt 等。相反，癌基因 miR 和 lncRNA 诱导 PD-1/PD-L1 轴。miR/PD-1 和 lncRNA/PD-1 信号通路的鉴定可以帮助我们找到癌症免疫疗法的有效药物，并指导我们对上述通路进行遗传操作。
