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癌症免疫治疗的内分泌副作用。

Endocrine side effects of cancer immunotherapy.

机构信息

Department of EndocrinologyInstituto do Cancer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Department of OncologyInstituto do Cancer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

出版信息

Endocr Relat Cancer. 2017 Dec;24(12):T331-T347. doi: 10.1530/ERC-17-0358. Epub 2017 Oct 12.

Abstract

Immune checkpoint inhibitors have recently become a cornerstone for the treatment of different advanced cancers. These drugs, represented mainly by monoclonal antibodies anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1) and anti-PD-1 ligand molecules (PD-L1 and L2), have the ability to reactivate the immune system against tumor cells, but can also trigger a myriad of autoimmune side effects, termed immune-related adverse events (irAEs). In particular, there are a number of endocrine-related irAEs. Current data from clinical trials show increased incidence of hypophysitis with CTLA4 inhibition and thyroid dysfunction with PD-(L)1 blockade. In addition, a few cases of type 1 diabetes mellitus and primary adrenal insufficiency have been reported. We discuss the incidence, clinical manifestations, diagnosis and management of immune-related endocrinopathies in this highly complex context of oncological patients in need of immunotherapies.

摘要

免疫检查点抑制剂最近已成为治疗多种晚期癌症的基石。这些药物主要代表为抗细胞毒性 T 淋巴细胞抗原 4(CTLA-4)、抗程序性细胞死亡蛋白 1(PD-1)和抗 PD-1 配体分子(PD-L1 和 L2)的单克隆抗体,它们具有重新激活免疫系统对抗肿瘤细胞的能力,但也会引发无数自身免疫副作用,称为免疫相关不良事件(irAEs)。特别是,有一些与内分泌相关的 irAEs。来自临床试验的现有数据显示 CTLA4 抑制会增加垂体炎的发病率,而 PD-(L)1 阻断会导致甲状腺功能障碍。此外,还报道了少数 1 型糖尿病和原发性肾上腺功能不全的病例。我们将在需要免疫治疗的肿瘤患者这一高度复杂的背景下,讨论免疫相关内分泌疾病的发病率、临床表现、诊断和治疗。

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