Division of Endocrinology, Diabetes and Metabolism, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Division of Hematology and Oncology, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
ESMO Open. 2021 Feb;6(1):100011. doi: 10.1016/j.esmoop.2020.100011. Epub 2021 Jan 4.
Immune checkpoint inhibitors (ICIs) are antibodies that target certain immune checkpoints (ICs), such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD-1) or its ligand (PD-L1), and have emerged as a powerful new tool for oncologists. As these immune checkpoints are crucial for immunological self-tolerance, such therapies can trigger autoimmune adverse effects. Endocrine complications are among the most common, including hypophysitis, thyroid dysfunction, diabetes mellitus and primary adrenal insufficiency, while autoimmune polyendocrine syndrome type 2 (APS-2) may also present. The aim of this article is to critically appraise the literature and present (i) the biological role and function of the main ICs, (ii) the use of ICIs in the treatment of various cancer types, (iii) the endocrine complications of cancer immunotherapy with ICIs and (iv) practical recommendations for screening and management of patients with such endocrinopathies in everyday clinical practice.
免疫检查点抑制剂(ICIs)是一类靶向某些免疫检查点(ICs)的抗体,如细胞毒性 T 淋巴细胞相关蛋白 4(CTLA-4)、程序性死亡受体 1(PD-1)或其配体(PD-L1),它们已成为肿瘤学家的有力新工具。由于这些免疫检查点对于免疫性自身耐受至关重要,因此这些疗法可能会引发自身免疫不良反应。内分泌并发症是最常见的并发症之一,包括垂体炎、甲状腺功能障碍、糖尿病和原发性肾上腺功能不全,同时也可能出现 2 型自身免疫性多内分泌腺综合征(APS-2)。本文的目的是批判性地评价文献,并介绍(i)主要 ICs 的生物学作用和功能,(ii)ICI 在治疗各种癌症类型中的应用,(iii)ICI 癌症免疫治疗的内分泌并发症,以及(iv)在日常临床实践中筛查和管理此类内分泌疾病患者的实用建议。