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免疫检查点抑制剂诱导的结肠炎:综述

Immune checkpoint inhibitor-induced colitis: A comprehensive review.

作者信息

Som Aniruddh, Mandaliya Rohan, Alsaadi Dana, Farshidpour Maham, Charabaty Aline, Malhotra Nidhi, Mattar Mark C

机构信息

Department of Internal Medicine, Medstar Washington Hospital Center, Washington, DC 20010, United States.

Department of Gastroenterology, MedStar Georgetown University Hospital, Washington, DC 20007, United States.

出版信息

World J Clin Cases. 2019 Feb 26;7(4):405-418. doi: 10.12998/wjcc.v7.i4.405.

Abstract

Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target down-regulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1. ICIs have revolutionized the treatment of a variety of malignancies. However, many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. The incidence of immune-mediated colitis (IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease, however more neutrophilic inflammation without chronic inflammation is usually present in IMC. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.

摘要

免疫检查点抑制剂(ICIs)是一类单克隆抗体,其作用靶点为抗癌免疫反应的下调因子:细胞毒性T淋巴细胞抗原4、程序性细胞死亡蛋白1及其配体程序性死亡配体1。ICIs彻底改变了多种恶性肿瘤的治疗方式。然而,也有许多免疫相关不良事件被报道,这些事件主要发生在免疫系统抑制作用减弱时,会影响包括胃肠道在内的多个器官,导致腹泻和结肠炎。免疫介导性结肠炎(IMC)的发生率在1%至25%之间,具体取决于ICIs的类型以及是否联合使用。在内镜检查和组织学检查中,IMC与炎症性肠病有显著重叠,但IMC通常存在更多的中性粒细胞炎症且无慢性炎症。对于2级或更严重的结肠炎,建议在暂停免疫治疗的同时使用皮质类固醇。约三分之一至三分之二的患者对类固醇耐药,可从英夫利昔单抗治疗中获益。最近发现维多珠单抗对类固醇和英夫利昔单抗耐药的病例有效。在4级结肠炎中,免疫治疗需永久停用,但在3级结肠炎中,这一决定存在争议。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0a/6397821/36cf644d2faf/WJCC-7-405-g001.jpg

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