Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
J Cell Physiol. 2019 Jun;234(6):8541-8549. doi: 10.1002/jcp.27816. Epub 2018 Dec 3.
Among the main promising systems to triggering therapeutic antitumor immunity is the blockade of immune checkpoints. Immune checkpoint pathways regulate the control and eradication of infections, malignancies, and resistance against a host of autoantigens. Initiation point of the immune response is T cells, which have a critical role in this pathway. As several immune checkpoints are initiated by ligand-receptor interactions, they can be freely blocked by antibodies or modulated by recombinant forms of ligands or receptors. Antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) were the first immunotherapeutics that achieved the US Food and Drug Administration approval. Preliminary clinical results with the blockers of additional immune checkpoint proteins, such as programmed cell death protein 1 (PD-1) indicate extensive and different chances to boost antitumor immunity with the objective of conferring permanent clinical effects. This study provides an overview of the immune checkpoint pathways, including CTLA-4, PD-1, lymphocyte activation gene 3, T-cell immunoglobulin and mucin domain 3, B7-H3, and diacylglycerol kinase α and implications of their inhibition in the cancer therapy.
在引发抗肿瘤免疫的主要有前途的系统中，免疫检查点的阻断是主要的。免疫检查点途径调节对感染、恶性肿瘤的控制和消除，以及对许多自身抗原的抵抗。免疫反应的起始点是 T 细胞，它在这个途径中起着关键作用。由于几个免疫检查点是由配体-受体相互作用引发的，因此它们可以被抗体自由阻断，也可以通过配体或受体的重组形式来调节。抗细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）的抗体是第一种获得美国食品和药物管理局批准的免疫疗法。阻断其他免疫检查点蛋白（如程序性细胞死亡蛋白 1（PD-1））的初步临床结果表明，有广泛而不同的机会可以增强抗肿瘤免疫，以达到赋予永久临床效果的目的。本研究概述了免疫检查点途径，包括 CTLA-4、PD-1、淋巴细胞激活基因 3、T 细胞免疫球蛋白和粘蛋白结构域 3、B7-H3、二酰基甘油激酶α 及其在癌症治疗中的抑制作用。
