Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
Immunol Rev. 2023 Sep;318(1):51-60. doi: 10.1111/imr.13242. Epub 2023 Jul 12.
Immune checkpoint inhibitors are now an established treatment in the management of a range of cancers. Their success means that their use is likely to increase in future in terms of the numbers of patients treated, the indications and the range of immune checkpoints targeted. They function by counteracting immune evasion by the tumor but, as a consequence, can breach self-tolerance at other sites leading to a range of immune-related adverse events. Included among these complications are a range of rheumatologic complications, including inflammatory arthritis and keratoconjunctivitis sicca. These superficially resemble immune-mediated rheumatic diseases (IMRDs) such as rheumatoid arthritis and Sjogren's disease but preliminary studies suggest they are clinically and immunologically distinct entities. However, there appear to be common processes that predispose to the development of both that may inform preventative interventions and predictive tools. Both groups of conditions highlight the centrality of immune checkpoints in controlling tolerance and how it can be restored. Here we will discuss some of these commonalities and differences between rheumatic irAEs and IMRDs.
免疫检查点抑制剂现已成为多种癌症治疗的标准疗法。随着接受治疗的患者人数、适应证和免疫检查点靶向范围的增加,预计其使用量在未来还会进一步增加。这些药物通过拮抗肿瘤的免疫逃逸起作用,但因此也可能在其他部位打破自身耐受,导致一系列免疫相关不良事件。这些并发症包括一系列风湿性并发症,包括炎症性关节炎和干燥性角膜结膜炎。这些疾病从表面上看类似于类风湿关节炎和干燥综合征等免疫介导的风湿性疾病(IMRDs),但初步研究表明,它们在临床上和免疫学上是不同的实体。然而,似乎存在一些共同的促使这些疾病发展的过程,这些过程可能为预防干预和预测工具提供信息。这两组疾病都强调了免疫检查点在控制耐受和恢复耐受方面的核心作用。在这里,我们将讨论风湿性免疫相关不良事件与 IMRD 之间的一些共同和不同之处。