Tocheva Anna S, Mor Adam
Department of Medicine, NYU School of Medicine, 450 E 29th Street, Room 806, New York, NY, 10016, USA.
Perlmutter Cancer Center, NYU School of Medicine, New York, NY, 10016, USA.
Curr Allergy Asthma Rep. 2017 Sep 27;17(10):72. doi: 10.1007/s11882-017-0740-z.
To limit excessive T cell-mediated inflammatory responses, the immune system has a milieu of inhibitory receptors, called immune checkpoints. Cancer cells have evolved to seize those inhibitory pathways and to prevent T cell-mediated killing of tumor cells. Therefore, immune checkpoint inhibitors (ICI) consisting of blocking antibodies against these receptors present an exciting avenue in the fight against cancer. The last decade has seen the implementation of ICI against a variety of cancer indications that have improved the overall anti-tumor responses and patient survival. However, inflammatory toxicities and autoimmunity are a significant adverse event of ICI therapies. In this review, we will discuss the biology of immune checkpoints, highlight research strategies that may help reduce the incidence of immune-related adverse events associated with ICI therapies, and also suggest investigational approaches to manipulate immune checkpoints to treat primary autoimmune disorders.
为了限制过度的T细胞介导的炎症反应，免疫系统拥有一系列抑制性受体，称为免疫检查点。癌细胞已经进化到利用这些抑制途径，以阻止T细胞介导的肿瘤细胞杀伤。因此，由针对这些受体的阻断抗体组成的免疫检查点抑制剂（ICI）成为对抗癌症的一个令人兴奋的途径。在过去十年中，针对多种癌症适应症的ICI已经得到应用，改善了总体抗肿瘤反应和患者生存率。然而，炎症毒性和自身免疫是ICI治疗的一个重大不良事件。在这篇综述中，我们将讨论免疫检查点的生物学特性，强调可能有助于降低与ICI治疗相关的免疫相关不良事件发生率的研究策略，并提出操纵免疫检查点以治疗原发性自身免疫性疾病的研究方法。
