CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Immune modulatory microRNAs in tumors, their clinical relevance in diagnosis and therapy.
Immune modulatory microRNAs in tumors, their clinical relevance in diagnosis and therapy.
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在过去几年中,随着接受不同免疫治疗药物治疗的癌症患者预期寿命不断延长,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控肿瘤生长的重要性日益凸显。
然而,肿瘤常常逃避免疫监视,这是通过不同机制实现的。近期研究表明,小型非编码 RNA,如 microRNA(miRNA),在免疫调节分子的转录后调控中发挥重要作用。多种方法已被用于鉴定靶向参与逃避免疫识别基因的 miRNA,包括靶向 CTLA-4、PD-L1、HLA-G、主要组织相容性 I 类抗原加工机制(APM)组分以及肿瘤中其他免疫应答相关基因的 miRNA。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,能够区分肿瘤分期并预测患者预后以及对(免疫)治疗的应答和耐药性;(2)治疗肿瘤患者的治疗靶点。本综述总结了 miRNA 在肿瘤介导的免疫逃逸中的作用,讨论了其作为诊断、预后和预测工具的潜力,以及其作为治疗手段的应用,包括替代应用方法,如CAR-T 细胞。
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.
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