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检查点抑制剂在自身免疫性疾病中的作用:与癌症相比的异同

英文原题:The Role of Checkpoint Inhibitors in Autoimmune Diseases: Similarities and Differences Compared with Cancer.

查看英文原题

The Role of Checkpoint Inhibitors in Autoimmune Diseases: Similarities and Differences Compared with Cancer.

PubMed 2022/01/01(内容时间) Crit Rev Immunol Q4 · IF 1.8(JCR 2025)

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中文摘要

程序性细胞死亡-1(PD-1)免疫抑制性受体的表达见于T细胞、B细胞、自然杀伤(NK)细胞和髓系细胞。当T细胞通过T细胞受体识别肽-主要组织相容性复合体(MHC)以及共刺激信号被激活后,包括PD-1在内的检查点被激活以调控T细胞。由于在小鼠模型中发现PD-1表达降低与外周耐受破坏相关,并表现出自身免疫病特征,因此该受体可能是自身免疫的重要治疗靶点。

此外,在自身免疫病患者中可见外周血NK细胞数量减少和细胞毒性降低,以及NK细胞活化性受体表达和细胞因子分泌的改变。因此,在本综述中我们讨论PD-1在NK细胞和T细胞中功能与自身免疫的相关性,并展示其在自身免疫病和癌症中功能的相似性与差异。

因此,PD-1可以被靶向以相应地治疗每种疾病实体。在癌症中,PD-1的功能可以被阻断以增强免疫激活,而在自身免疫病中其功能可以被增强以阻断过度亢进的免疫功能。

然而,我们远未理解该受体在复杂组织微环境中的确切功能,需要进一步研究以确定其在疾病不同阶段以及免疫效应细胞成熟不同阶段的功能。

展开英文摘要原文

Programmed cell death-1 (PD-1) immunoinhibitory receptor expression is found on T cells, B cells, natural killer (NK) cells, and myeloid cells. Upon activation of T cells through peptide-major histocompatibility complex (MHC) engagement of the T cell receptor and costimulatory signaling, checkpoints including PD-1 are activated to regulate T cells.

Since decreased expression of PD-1 in mice model was found to be associated with breakdown of peripheral tolerance, and demonstrated autoimmune disease characteristic, this receptor may be important therapeutic target for autoimmunity.

In addition, decreased NK cell numbers and cytotoxicity in peripheral blood and altered expression of activating receptors and cytokine secretion of NK cells was seen in autoimmune disease patients.

Therefore, in this review we discuss the relevance of PD-1 function in NK and T cells in autoimmunity, and demonstrate similarities and differences of its function in autoimmune diseases and cancer.

Thus, PD-1 can be targeted to treat each disease entity accordingly. In cancer, the function of PD-1 can be blocked in order to enhance immune activation, whereas in autoimmune diseases it can be enhanced to block heightened immune function.

However, we are far from understanding the exact functioning of this receptor in a complex tissue microenvironment, and further studies are required to establish its function at different stages of the disease, and at different stages of the maturation of immune effectors.

论文信息

作者
Kaur K、Chen PC、Ko MW、Jewett A
第一作者单位
Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, University of California School of Dentistry, 10833 Le Conte Ave, 90095 Los Angeles, CA, USA.United States
通讯作者单位
Division of Oral Biology and Medicine, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, University of California School of Dentistry, 10833 Le Conte Ave, 90095 Los Angeles, CA, USA; The Jonsson Comprehensive Cancer Center, UCLA School of Dentistry and Medicine, Los Angeles, CA, USA.United States
文献类型
综述
期刊
Critical reviews in immunology2022
原文标识
PubMed 37017624 · DOI 10.1615/CritRevImmunol.2023047303