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免疫检查点抑制剂相关腹泻和结肠炎:概述。

Immune checkpoint inhibitor-induced diarrhea and colitis: an overview.

机构信息

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Department of Emergency Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

出版信息

Support Care Cancer. 2024 Sep 23;32(10):680. doi: 10.1007/s00520-024-08889-2.

Abstract

Immune checkpoint inhibitors (ICIs) have emerged as an integral component of the management of various cancers and have contributed to significant improvements in overall survival. Most available ICIs target anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4), and anti-programmed cell death 1/programmed cell death ligand 1 (anti-PD1/PDL1). Gastrointestinal immune-related adverse events remain a common complication of ICIs. The predominant manifestations include diarrhea and colitis, which often manifest concurrently as immune-mediated diarrhea and colitis (IMDC). Risk factors for developing these side effects include baseline gut microbiota, preexisting autoimmune disorders, such as inflammatory bowel disease, and type of neoplasm. The hallmark symptom of colitis is diarrhea which may be accompanied by mucus or blood in stools. Patients may also experience abdominal pain, fever, vomiting, and nausea. If not treated rapidly, ICI-induced colitis can lead to serious life-threatening complications. Current management is based on corticosteroids as first-line, and immunosuppressants like infliximab or vedolizumab for refractory cases. Microbiota transplantation and specific cytokines and lymphocyte replication inhibitors are being investigated. Optimal patient care requires maintaining a balance between treatment toxicity and efficacy, hence the aim of this review is to enhance readers' comprehension of the gastrointestinal adverse events associated with ICIs, particularly IMDC. In addition to identifying the risk factors, we discuss the incidence, clinical presentation, workup, and management options of IMDC.

摘要

免疫检查点抑制剂(ICIs)已成为各种癌症治疗的重要组成部分,显著提高了总体生存率。大多数可用的 ICI 靶向抗细胞毒性 T 淋巴细胞相关蛋白 4(抗 CTLA4)和抗程序性细胞死亡 1/程序性细胞死亡配体 1(抗 PD1/PDL1)。胃肠道免疫相关不良事件仍然是 ICI 的常见并发症。主要表现包括腹泻和结肠炎,它们通常同时表现为免疫介导的腹泻和结肠炎(IMDC)。发生这些副作用的危险因素包括基线肠道微生物群、先前存在的自身免疫性疾病(如炎症性肠病)和肿瘤类型。结肠炎的标志性症状是腹泻,粪便中可能伴有粘液或血液。患者还可能出现腹痛、发热、呕吐和恶心。如果不迅速治疗,ICI 诱导的结肠炎可导致严重的危及生命的并发症。目前的治疗基于皮质类固醇作为一线治疗,对于难治性病例使用英夫利昔单抗或维得利珠单抗等免疫抑制剂。正在研究微生物群移植和特定细胞因子和淋巴细胞复制抑制剂。最佳的患者护理需要在治疗毒性和疗效之间取得平衡,因此,本综述的目的是增强读者对与 ICI 相关的胃肠道不良事件的理解,特别是 IMDC。除了确定危险因素外,我们还讨论了 IMDC 的发生率、临床表现、检查和治疗选择。

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