免疫检查点是指能调节机体免疫细胞活化和免疫耐受的共刺激和共抑制信号分子,其中共抑制信号分子会降低T细胞的抗肿瘤活性,造成肿瘤的免疫逃逸。美国科学家JamesP.Allison和日本科学家Tasuku Honjo分别发现了两个重要的共抑制信号分子——CTLA-4和PD-1,验证了针对二者的抑制剂抗体产生的抗肿瘤活性,为癌症治疗提供了新思路、新手段,并因此获得2018年的诺贝尔生理学或医学奖。介绍了获奖者及其研究经历,解读了肿瘤与T细胞免疫的机理,分析了免疫检查点药物发展的现状,展望了免疫检查点研究的方向。
Immune checkpoints, known as regulators of the immune system, are crucial to self-tolerance. The inhibitory checkpoint molecules function as brakes on the T cells, inhibiting immune activation, which contributes to tumor immune escape. James P. Allison and Tasuku Honjo individually studied two of the inhibitory checkpoint molecules, CTLA-4 and PD-1, showed their inhibitor antibodies' anti-tumor effect, provided new strategies for cancer therapy, and therefore won the 2018 Nobel Prize in Physiology or Medicine. In this paper, we introduce the laureates and their research experiences, interpret the mechanism of tumor and T-cell immunity, analyze the development status of checkpoint therapy, and finally predict the research direction of immune checkpoint.
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