Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, United States.
Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA, United States.
J Autoimmun. 2017 May;79:1-3. doi: 10.1016/j.jaut.2017.02.004. Epub 2017 Feb 27.
Immune checkpoint pathways modulate the T cell response to ensure their dual function in maintaining health, eradicating or controlling malignancy and infection, as well as tolerating host autoantigens. Dysregulation of the checkpoint pathways may lead to development of cancer or persistent infection, or alternately, autoimmune diseases. Currently available treatments for autoimmune diseases, such as steroid and nonsteroid immunosuppressive medicines, have limited efficacy. Checkpoint-based immunotherapy, designed to directly block the activation pathway or agitate the inhibitory pathway of autoreactive T cells, is a promising therapeutic strategy for restoring T cell tolerance in autoimmune diseases. A major challenge in developing the checkpoint-based therapy for autoimmune diseases is identifying pathways that will minimize the induction of adverse global immune suppression that impairs the host protective immunity against cancer and microbial pathogens. Therefore research efforts should focus on increasing the organ or antigen specificity of such therapies.
免疫检查点途径调节 T 细胞反应，以确保其在维持健康、消除或控制恶性肿瘤和感染以及耐受宿主自身抗原方面的双重功能。检查点途径的失调可能导致癌症或持续感染的发展，或者相反，导致自身免疫性疾病。目前用于自身免疫性疾病的治疗方法，如类固醇和非类固醇免疫抑制药物，疗效有限。基于检查点的免疫疗法旨在直接阻断自身反应性 T 细胞的激活途径或激活抑制途径，是恢复自身免疫性疾病中 T 细胞耐受的一种有前途的治疗策略。在为自身免疫性疾病开发基于检查点的治疗方法方面面临的主要挑战是确定哪些途径将最大限度地减少诱导不良的全身免疫抑制，从而损害宿主对癌症和微生物病原体的保护性免疫。因此，研究工作应侧重于提高此类疗法的器官或抗原特异性。
