Key questions about the checkpoint blockade-are microRNAs an answer?

作     者：Mihnea Dragomir Baoqing Chen Xiao Fu George A.Calin 

作者机构：Department of Experimental TherapeuticsThe University of Texas MD Anderson Cancer Center Research Center for Functional GenomicsBiomedicine and Translational MedicineIuliu Hatieganu University of Medicine and Pharmacy Department of SurgeryFundeni Clinical HospitalCarol Davila University of Medicine and Pharmacy Center for RNA Interference and Non-coding RNAsThe University of Texas MD Anderson Cancer Center 

出 版 物：《Cancer Biology & Medicine》 (癌症生物学与医学（英文版）)

年 卷 期：2018年第15卷第2期

页      面：103-115页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by National Institutes of Health (NIH/NCATS) grant UH3TR00943-01 through the NIH Common Fund, Office of Strategic Coordination(OSC) the NIH/NCI grant 1 R01 CA182905-01 a U54 grant-UPR/MDACC Partnership for Excellence in Cancer Research 2016 Pilot Project a Team DOD (Grant No.CA160445P1) grant a Ladies Leukemia League grant a CLL Moonshot Flagship project a SINF 2017 grant the Estate of C.G.Johnson,Jr. supported by a POC grant, entitled "Clinical and economical impact of personalized targeted anti-microRNA therapies in reconverting lung cancer chemoresistance"-CANTEMIR, Competitively Operational Program, 2014-2020, Grant No.35/01.09.2016,My SMIS 103375 

主　　题：检查点 封锁 癌症治疗 询问 免疫力 治疗学 RNA 管理局 

摘      要：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. Micro RNAs 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.