Institute for Medical Immunology, Martin Luther University Halle Wittenberg, Halle, Germany.
Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany.
J Immunother Cancer. 2024 Aug 29;12(8):e009774. doi: 10.1136/jitc-2024-009774.
The importance of the immune system in regulating tumor growth by inducing immune cell-mediated cytotoxicity associated with patients' outcomes has been highlighted in the past years by an increasing life expectancy in patients with cancer on treatment with different immunotherapeutics. However, tumors often escape immune surveillance, which is accomplished by different mechanisms. Recent studies demonstrated an essential role of small non-coding RNAs, such as microRNAs (miRNAs), in the post-transcriptional control of immune modulatory molecules. Multiple methods have been used to identify miRNAs targeting genes involved in escaping immune recognition including miRNAs targeting CTLA-4, PD-L1, HLA-G, components of the major histocompatibility class I antigen processing machinery (APM) as well as other immune response-relevant genes in tumors. Due to their function, these immune modulatory miRNAs can be used as (1) diagnostic and prognostic biomarkers allowing to discriminate between tumor stages and to predict the patients' outcome as well as response and resistance to (immuno) therapies and as (2) therapeutic targets for the treatment of tumor patients. This review summarizes the role of miRNAs in tumor-mediated immune escape, discuss their potential as diagnostic, prognostic and predictive tools as well as their use as therapeutics including alternative application methods, such as chimeric antigen receptor T cells.
近年来，随着接受不同免疫疗法治疗的癌症患者的预期寿命增加，免疫系统通过诱导与患者预后相关的免疫细胞介导的细胞毒性来调节肿瘤生长的重要性已得到强调。然而，肿瘤通常会逃避免疫监视，这是通过不同的机制实现的。最近的研究表明，小非编码 RNA（如 microRNAs（miRNAs））在免疫调节分子的转录后控制中起着重要作用。已经使用多种方法来鉴定靶向参与逃避免疫识别的基因的 miRNAs，包括靶向 CTLA-4、PD-L1、HLA-G 的 miRNAs、主要组织相容性复合体 I 抗原加工机制 (APM) 的成分以及肿瘤中其他与免疫反应相关的基因。由于其功能，这些免疫调节 miRNA 可用作（1）诊断和预后生物标志物，可区分肿瘤分期，并预测患者的预后以及对（免疫）治疗的反应和耐药性，以及（2）治疗肿瘤患者的治疗靶点。这篇综述总结了 miRNAs 在肿瘤介导的免疫逃逸中的作用，讨论了它们作为诊断、预后和预测工具的潜力，以及它们作为治疗剂的用途，包括嵌合抗原受体 T 细胞等替代应用方法。
