The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2020,（4）
• 页码范围: 285-299
• 页数: 15页
• 语种: 英文

摘要

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-inhibitoryreceptors 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.