[Hematological immune-related adverse events of immune checkpoint inhibitors and their management].

Yoshiki Akatsuka
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Abstract

Immune checkpoints suppress inappropriate immune responses to self-molecules or cells. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) expressed in T cells are representative molecules involved in the immune checkpoint system. The recent advent of immune checkpoint inhibitors (ICIs) has drastically changed cancer immunotherapy because a substantial proportion of patients with advanced cancers have responded to ICIs and some of them have been cured. This benefit is due to T-cell rescue from immune suppression in their tumor microenvironment by blocking cluster of differentiation 80/CTLA-4 and PD-L1/PD-1 interactions. However, blocking these interactions also liberates T cells that are reactive to self-antigens from tolerance, resulting in the occurrence of autoimmune diseases, that is, immune-related adverse events. Although the primary target organs are the lungs, gastrointestinal tract, and endocrine glands, hematopoietic cells are also affected in 0.5-3% of patients, potentially resulting in anemia or thrombocytopenia. Because hematopoietic system homeostasis is critical to maintaining life support, the occurrence of grade 3-4 irAEs in the hematopoietic system is directly life-threatening. Herein, we review the relationship between ICIs and toxicities in patients with cancer and describe the characteristics and management strategies for hematological immune-related adverse events.
[免疫检查点抑制剂的血液免疫相关不良事件及其处理]。
免疫检查点抑制对自身分子或细胞的不适当免疫反应。T细胞中表达的细胞毒性T淋巴细胞相关蛋白4 (CTLA-4)和程序性细胞死亡蛋白1 (PD-1)是参与免疫检查点系统的代表性分子。最近出现的免疫检查点抑制剂(ICIs)已经彻底改变了癌症免疫治疗,因为相当大比例的晚期癌症患者对ICIs有反应,其中一些已经治愈。这种益处是由于t细胞通过阻断分化簇80/CTLA-4和PD-L1/PD-1相互作用而从肿瘤微环境中的免疫抑制中解脱出来。然而,阻断这些相互作用也会将对自身抗原有反应的T细胞从耐受性中解放出来,从而导致自身免疫性疾病的发生,即免疫相关的不良事件。虽然主要的靶器官是肺、胃肠道和内分泌腺,但0.5-3%的患者也会影响造血细胞,可能导致贫血或血小板减少症。由于造血系统稳态对维持生命支持至关重要,因此造血系统发生3-4级irae直接危及生命。在此,我们回顾了癌症患者的ICIs与毒性之间的关系,并描述了血液学免疫相关不良事件的特征和管理策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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