From the Department of Clinical Oncology, Manchester University NHS Foundation Trust, Manchester, United Kingdom.
Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston, Ontario, Canada.
Anesth Analg. 2021 Feb 1;132(2):374-383. doi: 10.1213/ANE.0000000000005029.
As part of immune surveillance, killer T lymphocytes search for cancer cells and destroy them. Some cancer cells, however, develop escape mechanisms to evade detection and destruction. One of these mechanisms is the expression of cell surface proteins which allow the cancer cell to bind to proteins on T cells called checkpoints to switch off and effectively evade T-cell-mediated destruction. Immune checkpoint inhibitors (ICIs) are antibodies that block the binding of cancer cell proteins to T-cell checkpoints, preventing the T-cell response from being turned off by cancer cells and enabling killer T cells to attack. In other words, ICIs restore innate antitumor immunity, as opposed to traditional chemotherapies that directly kill cancer cells. Given their relatively excellent risk-benefit ratio when compared to other forms of cancer treatment modalities, ICIs are now becoming ubiquitous and have revolutionized the treatment of many types of cancer. Indeed, the prognosis of some patients is so much improved that the threshold for admission for intensive care should be adjusted accordingly. Nevertheless, by modulating immune checkpoint activity, ICIs can disrupt the intricate homeostasis between inhibition and stimulation of immune response, leading to decreased immune self-tolerance and, ultimately, autoimmune complications. These immune-related adverse events (IRAEs) may virtually affect all body systems. Multiple IRAEs are common and may range from mild to life-threatening. Management requires a multidisciplinary approach and consists mainly of immunosuppression, cessation or postponement of ICI treatment, and supportive therapy, which may require surgical intervention and/or intensive care. We herein review the current literature surrounding IRAEs of interest to anesthesiologists and intensivists. With proper care, fatality (0.3%-1.3%) is rare.
作为免疫监视的一部分，杀伤性 T 淋巴细胞会寻找癌细胞并将其摧毁。然而，一些癌细胞会发展出逃避机制来躲避检测和破坏。其中一种机制是表达细胞表面蛋白，使癌细胞能够与 T 细胞上称为检查点的蛋白结合，从而关闭并有效地逃避 T 细胞介导的破坏。免疫检查点抑制剂（ICI）是一种抗体，可阻止癌细胞蛋白与 T 细胞检查点结合，防止 T 细胞反应被癌细胞关闭，并使杀伤性 T 细胞能够攻击。换句话说，ICI 恢复了先天抗肿瘤免疫，而不是传统的化疗药物直接杀死癌细胞。与其他癌症治疗方式相比，ICI 具有相对较好的风险效益比，因此现在已广泛应用，并彻底改变了许多类型癌症的治疗方法。事实上，由于某些患者的预后得到了极大改善，因此应该相应调整重症监护的入院标准。然而，通过调节免疫检查点的活性，ICI 可能会破坏免疫反应抑制和刺激之间的复杂平衡，导致免疫自身耐受降低，最终导致自身免疫并发症。这些与免疫相关的不良反应（IRAEs）可能几乎会影响所有身体系统。多种 IRAEs 很常见，可能从轻度到危及生命不等。管理需要多学科的方法，主要包括免疫抑制、停止或推迟 ICI 治疗以及支持性治疗，这可能需要手术干预和/或重症监护。我们在此回顾了麻醉师和重症监护医生感兴趣的 IRAEs 的现有文献。通过适当的护理，死亡率（0.3%-1.3%）是罕见的。
