Anticancer immunotherapy, in the form of immune checkpoint inhibition, is a paradigm shift that has transformed the care of patients with different types of solid and hematologic cancers. The most notable improvements have been seen in patients with melanoma, non-small-cell lung, bladder, renal, cervical, urotherial, and colorectal cancers, Merkel cell carcinoma, and Hodgkin lymphoma. Monoclonal antibodies (mAbs) targeting immune checkpoints (i.e., anti-CTLA: ipilimumab; anti-PD-1: nivolumab, pembrolizumab; anti-PD-L1: durvalumab, atezolizumab, avelumab) unleash the immune system against tumor cells targeting mainly T cells. Treatment with immune checkpoint inhibitors (ICIs) is associated with a variety of diverse and distinct immune-related adverse events (irAEs), reflecting the mechanistic underpinning of each target (i.e., CTLA-4, and PD-1/PD-L1 network). The most frequent endocrine irAEs associated with anti-PD-1 mAb treatment are thyroid dysfunctions, whereas hypophysitis is mostly linked to anti-CTLA-4 treatment. Type 1 diabetes mellitus and adrenalitis are rare irAEs. Combination therapy (anti-CTLA-4 plus anti-PD-1/PD-L1) can be associated with an increased risk and prevalence of endocrine irAEs. In this paper we discuss the pathophysiological and clinical aspects of irAEs with specific emphasis on endocrine irAEs associated with ICIs. With a growing number of patients treated with ICIs, a tight collaboration among oncologists, endocrinologists and immunologists appears necessary when the circumstances are more challenging and for better management of severe endocrine irAEs. Further investigations are urgently needed to better understand the mechanisms by which different ICIs can induce a variety of endocrine irAEs.

中文翻译：

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对与免疫检查点封锁相关的内分泌相关不良事件的新见解。

免疫检查点抑制形式的抗癌免疫疗法是一种范式转变，已经改变了对不同类型的实体和血液癌症患者的治疗。在患有黑素瘤，非小细胞肺癌，膀胱癌，肾癌，宫颈癌，尿道癌和结肠直肠癌，默克尔细胞癌和霍奇金淋巴瘤的患者中看到了最显着的改善。靶向免疫检查点的单克隆抗体（mAb）（例如，抗CTLA：​​伊匹木单抗；抗PD-1：尼古拉单抗，派姆单抗；抗PD-L1：杜鲁伐单抗，阿特珠单抗，阿伐单抗）释放针对主要靶向T细胞的肿瘤细胞的免疫系统。免疫检查点抑制剂（ICIs）的治疗与多种多样且独特的免疫相关不良事件（irAEs）相关，反映了每个靶标的机制基础（即CTLA-4，和PD-1 / PD-L1网络）。与抗PD-1 mAb治疗相关的最常见的内分泌irAE是甲状腺功能障碍，而垂体炎大多与抗CTLA-4治疗有关。1型糖尿病和肾上腺炎是罕见的irAE。联合治疗（抗CTLA-4加上抗PD-1 / PD-L1）可与内分泌irAE的风险和患病率增加相关。在本文中，我们讨论了irAEs的病理生理学和临床方面，特别侧重于与ICI相关的内分泌irAEs。随着越来越多的接受ICI治疗的患者，当情况更具挑战性并能更好地管理严重的内分泌irAE时，肿瘤学家，内分泌学家和免疫学家之间需要紧密合作。