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免疫 T 细胞和癌细胞中 PD-1/PD-L1 siRNA 递呈系统的综述。

A review of PD-1/PD-L1 siRNA delivery systems in immune T cells and cancer cells.

机构信息

Department of Pathobiology and Laboratory Sciences, North Khorasan University of Medical Sciences, Bojnurd, Iran.

Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran.

出版信息

Int Immunopharmacol. 2022 Oct;111:109022. doi: 10.1016/j.intimp.2022.109022. Epub 2022 Aug 17.

DOI:10.1016/j.intimp.2022.109022
PMID:35987146
Abstract

OBJECTIVES

Programmed cell death 1 (PD-1) is a member of the CD28/CTLA-4 family of inhibitory immunological checkpoint receptors that's also widely produced by exhausted T lymphocytes in an immunosuppressive tumor microenvironment. PD-1 binds to programmed death ligand (PD-L1) and suppresses anti-cancer activity of T lymphocytes. We examined the current literature on how siRNA delivery systems can be used to target PD-1 and PD-L1, as well as the anti-cancer mechanisms and challenges associated with siRNA molecules. We look at studies that use program death 1 siRNA or program death 1 ligand siRNA to treat cancer. Several databases have been used for this purpose, including NCBI, Scopus, and Google Scholar.

KEY FINDINGS

This study looked at several methods for delivering siRNA to immune cells and cancer cells. According to these findings, suppressing PD-1 in T cells increases T lymphocyte activity. PD-L1 suppression in DCs improves antigen presentation and co-stimulatory signals on their surface, resulting in T cell activation. Chemotherapy resistance and cancer cell suppression of T cells are reduced when PD-L1/2 is suppressed in cancer cells.

CONCLUSION

The findings of this study indicated that several strategies for siRNA transfection to immune and cancer cells have been evaluated in recent decades, some of which effectively transfect siRNA to target cells, and defined PD-1 siRNA as a promising strategy for cancer treatment.

摘要

目的

程序性细胞死亡蛋白 1(PD-1)是 CD28/CTLA-4 家族抑制性免疫检查点受体的成员,在免疫抑制性肿瘤微环境中也广泛由耗竭的 T 淋巴细胞产生。PD-1 与程序性死亡配体(PD-L1)结合,抑制 T 淋巴细胞的抗癌活性。我们检查了目前关于 siRNA 递送系统如何用于靶向 PD-1 和 PD-L1 以及与 siRNA 分子相关的抗癌机制和挑战的文献。我们研究了使用程序性死亡 1 siRNA 或程序性死亡 1 配体 siRNA 治疗癌症的研究。为此目的使用了几个数据库,包括 NCBI、Scopus 和 Google Scholar。

主要发现

本研究探讨了将 siRNA 递送至免疫细胞和癌细胞的几种方法。根据这些发现,抑制 T 细胞中的 PD-1 可增加 T 淋巴细胞的活性。抑制 DC 中的 PD-L1 可改善其表面的抗原呈递和共刺激信号,从而激活 T 细胞。抑制癌细胞中的 PD-L1/2 可降低化疗耐药性和癌细胞对 T 细胞的抑制作用。

结论

本研究的结果表明,近几十年来已经评估了几种将 siRNA 转染至免疫和癌细胞的策略,其中一些策略可有效地将 siRNA 转染至靶细胞,并将 PD-1 siRNA 定义为一种有前途的癌症治疗策略。

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