免疫检查点抑制剂的内分泌免疫相关不良反应。
Endocrine immune-related adverse effects of immune-checkpoint inhibitors.
发表日期：2023 Sep 08
作者：
Viola Trevisani, Lorenzo Iughetti, Laura Lucaccioni, Barbara Predieri
来源：
CYTOKINE & GROWTH FACTOR REVIEWS
摘要：
免疫检查点抑制剂治疗调节免疫系统对抗癌症的反应。这种治疗影响的两条通路是CTLA4和PD-1/PD-L1通路。ICI治疗可以触发自身免疫不良反应，即免疫相关不良事件（irAEs）。本综述聚焦于影响内分泌系统的irAEs。本综述揭示了这些药物使用的通路，重点关注其潜在发病机制。事实上，irAEs的病理生理涉及细胞自身免疫、体液免疫、细胞因子、趋化因子和遗传因素之间的可能相互作用。所考察的内分泌系统irAEs包括甲状腺功能障碍、免疫相关性垂体炎、糖尿病、外周肾上腺功能不全和甲状旁腺功能减退症。目前在检查点抑制剂的内分泌irAEs方面仍需深入研究。未来，检查点抑制剂将越来越多地被应用于治疗，因此找到适当的诊断治疗方案对于irAEs尤其是内分泌irAEs来说至关重要，因其是不可逆转且需终身替代治疗。
Immune-checkpoint inhibitor therapy modulates the response of the immune system acting against cancer. Two pathways impacted by this kind of treatment are the CTLA4 and the PD-1/PD-L1 pathways. ICI therapy can trigger autoimmune adverse effects, known as immune-related Adverse Events (irAEs).This review focuses on irAEs which affect the endocrine system. This review elucidates the pathways used by these drugs with a focus on the hypothetical pathogenesis at their basis. In fact, the pathophysiology of irAEs concerns the possibility of an interaction between cellular autoimmunity, humoral immunity, cytokines, chemokines, and genetics. The endocrine irAEs examined are thyroid dysfunctions, immune related-hypophysitis, diabetes, peripheral adrenal insufficiency, and hypoparathyroidism.There is still much to investigate in endocrine irAES of checkpoint inhibitors. In the future, checkpoint inhibitors will be increasingly utilized therapies, and therefore it is crucial to find the proper diagnostic-therapeutic program for irAEs, especially as endocrine irAEs are nonreversible and require lifelong replacement therapies.