免疫检查点抑制剂(ICIs),一种新的抗肿瘤治疗方式,是针对某些免疫检查点(IC)的单克隆抗体,这些免疫检查点通过靶向重新激活T细胞以实现抗肿瘤免疫,绑定,和阻塞IC。针对IC细胞毒性T淋巴细胞抗原和程序性死亡受体1的靶向抑制性抗体已在癌症患者中证明了功效和持久的抗肿瘤活性。IC可以预防自身免疫反应。然而,ICI可能会破坏IC特性并引发涉及各种器官系统的自身免疫相关不良反应,包括心血管,肺,胃肠,肾,肌肉骨骼,真皮,和内分泌系统。大约10%的患者对靶器官如甲状腺有损害,垂体,胰腺,和肾上腺发展内分泌系统免疫相关的不良事件(irAE),如甲状腺功能障碍,垂体炎症,糖尿病,和原发性肾上腺功能不全.然而,免疫疗法相关内分泌系统irAE的症状可能是非特异性的,与其他治疗相关的不良反应相似,如果不能及早识别它们,可能会导致死亡。及时检测和治疗免疫疗法相关的内分泌irAE对于提高免疫疗法的疗效至关重要。预后,以及患者的生活质量。本研究旨在回顾ICIs引起内分泌不良反应的机制,为制定适当的管理方案提供指导。这里,我们讨论了(1)IC在肿瘤发生和发展中的生物学机制,专注于细胞毒性T淋巴细胞抗原和程序性细胞死亡-1/程序性细胞死亡-配体1;和(2)流行病学,临床症状,诊断,以及四种免疫治疗相关内分泌并发症的治疗。
Immune checkpoint inhibitors (ICIs), a novel anti-tumor therapeutic modality, are monoclonal antibodies targeting certain immune checkpoints (ICs) that reactivate T cells to achieve anti-tumor immunity by targeting, binding, and blocking ICs. Targeted inhibitory antibodies against the ICs cytotoxic T-lymphocyte antigen and programmed death receptor-1 have demonstrated efficacy and durable anti-tumor activity in patients with cancer. ICs may prevent autoimmune reactions. However, ICIs may disrupt ICs properties and trigger autoimmune-related adverse reactions involving various organ systems including the cardiovascular, pulmonary, gastrointestinal, renal, musculoskeletal, dermal, and endocrine systems. Approximately 10% of patients with damage to target organs such as the thyroid, pituitary, pancreas, and adrenal glands develop endocrine system immune-related adverse events (irAEs) such as thyroid dysfunction, pituitary gland inflammation, diabetes mellitus, and primary adrenal insufficiency. However, the symptoms of immunotherapy-associated endocrine system irAEs may be nonspecific and similar to those of other treatment-related adverse reactions, and failure to recognize them early may lead to death. Timely detection and treatment of immunotherapy-associated endocrine irAEs is essential to improve the efficacy of immunotherapy, prognosis, and the quality of life of patients. This study aimed to review the mechanisms by which ICIs cause endocrine irAEs providing guidance for the development of appropriate management protocols. Here, we discuss (1) the biological mechanisms of ICs in tumorigenesis and progression, focusing on cytotoxic T-lymphocyte antigen and programmed cell death-1/programmed cell death-ligand 1; and (2) the epidemiology, clinical symptoms, diagnosis, and treatment of four immunotherapy-related endocrine complications.