Shadbad Mahdi Abdoli, Ghorbaninezhad Farid, Hassanian Hamidreza, Ahangar Noora Karim, Hosseinkhani Negar, Derakhshani Afshin, Shekari Najibeh, Brunetti Oronzo, Silvestris Nicola, Baradaran Behzad
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Front Med (Lausanne). 2022 Oct 31;9:1027758. doi: 10.3389/fmed.2022.1027758. eCollection 2022.
The programmed death-ligand 1 (PD-L1)/PD-1 axis is one of the well-established inhibitory axes in regulating immune responses. Besides the significance of tumor-intrinsic PD-L1 expression in immune evasion, its oncogenic role has been implicated in various malignancies, like non-small cell lung cancer (NSCLC). As small non-coding RNAs, microRNAs (miRs) have pivotal roles in cancer biology. The current study aimed to systematically review the current knowledge about the significance of PD-L1-inhibiting miRs in NSCLC inhibition and their underlying mechanisms.
We conducted the current scoping review based on the PRISMA-ScR statement. We systematically searched Embase, Scopus, Web of Science, PubMed, Ovid, EBSCO, ProQuest, Cochrane Library, African Index Medicus, and Pascal-Francis up to 4 April 2021. We also performed tumor bulk RNA sequencing and single-cell RNA sequencing to further the current knowledge of the non-coding RNA-mediated tumor-intrinsic PD-L1 regulation and the PD-L1/PD-1 axis in NSCLC.
The ectopic expression of hsa-miR-194-5p, hsa-miR-326, hsa-miR-526b-3p, hsa-miR-34a-5p, hsa-miR-34c-5p, hsa-miR-138-5p, hsa-miR-377-3p, hsa-let-7c-5p, hsa-miR-200a-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, and hsa-miR-197-3p, as PD-L1-inhibiting miR, inhibits NSCLC development. These PD-L1-inhibiting miRs can substantially regulate the cell cycle, migration, clonogenicity, invasion, apoptosis, tumor chemosensitivity, and host anti-tumoral immune responses. Based on single-cell RNA sequencing results, PD-L1 inhibition might liberate the tumor-infiltrated CD8 T-cells and dendritic cells (DCs)-mediated anti-tumoral immune responses disrupting the PD-L1/PD-1 axis.
Given the promising preclinical results of these PD-L1-inhibiting miRs in inhibiting NSCLC development, their ectopic expression might improve NSCLC patients' prognosis; however, further studies are needed to translate this approach into clinical practice.
程序性死亡配体1（PD-L1）/程序性死亡受体1（PD-1）轴是调节免疫反应中已确立的抑制轴之一。除了肿瘤内源性PD-L1表达在免疫逃逸中的重要性外，其致癌作用在各种恶性肿瘤中也有涉及，如非小细胞肺癌（NSCLC）。作为小非编码RNA，微小RNA（miRs）在癌症生物学中具有关键作用。本研究旨在系统综述目前关于抑制PD-L1的miRs在NSCLC抑制中的意义及其潜在机制的知识。
我们根据PRISMA-ScR声明进行了本次范围综述。我们系统检索了截至2021年4月4日的Embase、Scopus、科学网、PubMed、Ovid、EBSCO、ProQuest、Cochrane图书馆、非洲医学索引和Pascal-Francis。我们还进行了肿瘤整体RNA测序和单细胞RNA测序，以进一步了解非编码RNA介导的肿瘤内源性PD-L1调节以及NSCLC中的PD-L1/PD-1轴。
作为抑制PD-L1的miR，hsa-miR-194-5p、hsa-miR-326、hsa-miR-526b-3p、hsa-miR-34a-5p、hsa-miR-34c-5p、hsa-miR-138-5p、hsa-miR-377-3p、hsa-let-7c-5p、hsa-miR-200a-3p、hsa-miR-200b-3p、hsa-miR-200c-3p和hsa-miR-197-3p的异位表达可抑制NSCLC的发展。这些抑制PD-L1的miRs可显著调节细胞周期、迁移、克隆形成、侵袭、凋亡、肿瘤化学敏感性和宿主抗肿瘤免疫反应。基于单细胞RNA测序结果，抑制PD-L1可能会释放肿瘤浸润的CD8 T细胞和树突状细胞（DCs）介导的抗肿瘤免疫反应，破坏PD-L1/PD-1轴。
鉴于这些抑制PD-L1的miRs在抑制NSCLC发展方面有前景良好的临床前结果，其异位表达可能会改善NSCLC患者的预后；然而，需要进一步研究将这种方法转化为临床实践。
