Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Curr Opin Immunol. 2023 Feb;80:102283. doi: 10.1016/j.coi.2023.102283. Epub 2023 Jan 28.
Immune checkpoint receptors such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), and T cell immunoglobulin and ITIM domain (TIGIT) have distinct and overlapping inhibitory functions that regulate Tcell activation, differentiation, and function. These inhibitory receptors also mediate tolerance, and dysregulation of these receptors can result in a breach of tolerance and the development of autoimmune syndromes. Similarly, antibody blockade of immune checkpoint receptors or their ligands for cancer immunotherapy may trigger a spectrum of organ inflammation that resembles autoimmunity, termed immune-related adverse events (irAE). In this review, we discuss recent advances in the regulation of autoimmunity by immune checkpoint receptors. We highlight coordinated gene expression programs linking checkpoint receptors, heterogeneity within autoreactive T-cell populations, parallels between irAE and autoimmunity, and bidirectional functional interactions between immune checkpoint receptors and their ligands.
免疫检查点受体，如程序性细胞死亡蛋白 1（PD-1）、细胞毒性 T 淋巴细胞相关蛋白 4（CTLA-4）、淋巴细胞激活基因 3（LAG-3）和 T 细胞免疫球蛋白和 ITIM 结构域（TIGIT），具有独特和重叠的抑制功能，可调节 T 细胞的激活、分化和功能。这些抑制性受体还介导耐受，这些受体的失调可能导致耐受破裂和自身免疫综合征的发展。同样，针对癌症免疫治疗的免疫检查点受体或其配体的抗体阻断可能会引发类似于自身免疫的一系列器官炎症，称为免疫相关不良事件（irAE）。在这篇综述中，我们讨论了免疫检查点受体对自身免疫的调控的最新进展。我们强调了连接检查点受体的协调基因表达程序、自身反应性 T 细胞群体内的异质性、irAE 和自身免疫之间的平行性，以及免疫检查点受体与其配体之间的双向功能相互作用。
