Dragomir Mihnea, Chen Baoqing, Fu Xiao, Calin George A
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca 400012, Romania.
Cancer Biol Med. 2018 May;15(2):103-115. doi: 10.20892/j.issn.2095-3941.2018.0006.
The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stage cancers. There are already multiple FDA approved checkpoint inhibitors and many other agents are undergoing phase 2 and early phase 3 clinical trials. The therapeutic indication of immune checkpoint inhibitors expanded in the last years, but still remains unclear who can benefit. MicroRNAs are small RNAs with no coding potential. By complementary pairing to the 3' untranslated region of messenger RNA, microRNAs exert posttranscriptional control of protein expression. A network of microRNAs directly and indirectly controls the expression of checkpoint receptors and several microRNAs can target multiple checkpoint molecules, mimicking the therapeutic effect of a combined immune checkpoint blockade. In this review, we will describe the microRNAs that control the expression of immune checkpoints and we will present four specific issues of the immune checkpoint therapy in cancer: (1) imprecise therapeutic indication, (2) difficult response evaluation, (3) numerous immunologic adverse-events, and (4) the absence of response to immune therapy. Finally, we propose microRNAs as possible solutions for these pitfalls. We consider that in the near future microRNAs could become important therapeutic partners of the immune checkpoint therapy.
免疫检查点阻断剂引入癌症治疗领域引发了晚期癌症治疗模式的变革。目前已有多种获得美国食品药品监督管理局（FDA）批准的检查点抑制剂，许多其他药物正处于2期和早期3期临床试验阶段。近年来，免疫检查点抑制剂的治疗适应证有所扩展，但仍不清楚哪些患者能够从中获益。微小RNA是一类无编码能力的小RNA。微小RNA通过与信使RNA的3'非翻译区互补配对，对蛋白质表达进行转录后调控。微小RNA网络直接或间接控制检查点受体的表达，几种微小RNA可靶向多个检查点分子，模拟联合免疫检查点阻断的治疗效果。在本综述中，我们将描述控制免疫检查点表达的微小RNA，并阐述癌症免疫检查点治疗中的四个具体问题：（1）治疗适应证不明确；（2）反应评估困难；（3）免疫相关不良事件众多；（4）对免疫治疗无反应。最后，我们提出将微小RNA作为解决这些问题的可能方案。我们认为，在不久的将来，微小RNA可能成为免疫检查点治疗的重要治疗伙伴。
