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聚焦免疫检查点抑制剂相关肠道炎症:从发病机制到治疗方法。

Focus on Immune Checkpoint Inhibitors-related Intestinal Inflammation: From Pathogenesis to Therapeutical Approach.

机构信息

UOS Malattie Infiammatorie Croniche Intestinali, Centro di Malattie dell'Apparato Digerente (CEMAD), Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy.

UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Roma, 00168, Italy.

出版信息

Inflamm Bowel Dis. 2024 Jun 3;30(6):1018-1031. doi: 10.1093/ibd/izad229.

Abstract

Recently, antitumor immunotherapies have witnessed a breakthrough with the emergence of immune checkpoint inhibitors (ICIs) including programmed cell death-1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. Unfortunately, the use of ICIs has also led to the advent of a novel class of adverse events that differ from those of classic chemotherapeutics and are more reminiscent of autoimmune diseases, the immune-related adverse events (IRAEs). Herein, we performed an insight of the main IRAEs associated with ICIs, focusing on gastroenterological IRAEs and specifically on checkpoint inhibitor colitis, which represents the most widely reported IRAE to date. We comprehensively dissected the current evidence regarding pathogenesis, diagnosis, and management of ICIs-induced colitis, touching upon also on innovative therapies.

摘要

最近,随着免疫检查点抑制剂(ICIs)的出现,包括程序性细胞死亡蛋白-1(PD-1)、程序性细胞死亡配体 1(PD-L1)和细胞毒性 T 淋巴细胞相关抗原 4(CTLA-4)抑制剂,抗肿瘤免疫疗法取得了突破。不幸的是,ICIs 的使用也导致了一类新型的不良事件的出现,这些不良事件与经典的化疗药物不同,更类似于自身免疫性疾病,即免疫相关不良事件(IRAEs)。在此,我们深入探讨了与 ICIs 相关的主要 IRAEs,重点关注胃肠道 IRAEs,特别是检查点抑制剂结肠炎,这是迄今为止报道最多的 IRAE。我们全面剖析了目前关于 ICI 诱导结肠炎的发病机制、诊断和治疗的证据,同时也涉及到创新疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8323/11144981/1332d2657912/izad229_fig4.jpg

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