Co-inhibitory receptors are important regulators of T-cell function that define the balance between tolerance and autoimmunity. The immune regulatory function of co-inhibitory receptors, including CTLA-4, PD-1, TIM-3, TIGIT, and LAG-3, was first discovered in the setting of autoimmune disease models, in which their blockade or deficiency resulted in induction or exacerbation of the disease. Later on, co-inhibitory receptors on lymphocytes have also been found to influence outcomes in tumor and chronic viral infection settings. These receptors suppress T-cell function in the tumor microenvironment (TME), thereby making the T cells dysfunctional. Based on this observation, blockade of co-inhibitory receptors (also known as checkpoint molecules) has emerged as a successful treatment option for a number of human cancers. However, severe autoimmune-like side effects limit the use of therapeutics that block individual or combinations of co-inhibitory receptors for cancer treatment. In this review we provide an overview of the role of co-inhibitory receptors in autoimmunity and anti-tumor immunity. We then discuss current approaches and future directions to leverage our knowledge of co-inhibitory receptors to target them in tumor immunity without inducing autoimmunity.

中文翻译：

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共抑制受体的阴阳：没有自身免疫的抗肿瘤免疫。

共抑制受体是 T 细胞功能的重要调节剂，它定义了耐受性和自身免疫之间的平衡。共抑制受体（包括 CTLA-4、PD-1、TIM-3、TIGIT 和 LAG-3）的免疫调节功能最初是在自身免疫性疾病模型中发现的，它们的阻断或缺陷导致诱导或病情加重。后来，还发现淋巴细胞上的共抑制受体会影响肿瘤和慢性病毒感染环境的结果。这些受体抑制肿瘤微环境 (TME) 中的 T 细胞功能，从而使 T 细胞功能失调。基于这一观察，共抑制受体（也称为检查点分子）的阻断已成为许多人类癌症的成功治疗选择。然而，严重的自身免疫样副作用限制了阻断单个或多个共抑制受体组合的疗法在癌症治疗中的应用。在这篇综述中，我们概述了共抑制受体在自身免疫和抗肿瘤免疫中的作用。然后，我们讨论了当前的方法和未来的方向，以利用我们对共抑制受体的知识在肿瘤免疫中靶向它们而不诱导自身免疫。