Department of Anatomy, Histology, and Embryology, Semmelweis University, Tuzolto St. 58, 1094 Budapest, Hungary.
Translational Medicine Institute, Semmelweis University, 1094 Budapest, Hungary.
Int J Mol Sci. 2023 Feb 1;24(3):2769. doi: 10.3390/ijms24032769.
Immune checkpoint inhibitors (ICIs) have changed how we think about tumor management. Combinations of anti-programmed death ligand-1 (PD-L1) immunotherapy have become the standard of care in many advanced-stage cancers, including as a first-line therapy. Aside from improved anti-tumor immunity, the mechanism of action of immune checkpoint inhibitors (ICIs) exposes a new toxicity profile known as immune-related adverse effects (irAEs). This novel toxicity can damage any organ, but the skin, digestive and endocrine systems are the most frequently afflicted. Most ICI-attributed toxicity symptoms are mild, but some are severe and necessitate multidisciplinary side effect management. Obtaining knowledge on the various forms of immune-related toxicities and swiftly changing treatment techniques to lower the probability of experiencing severe irAEs has become a priority in oncological care. In recent years, there has been a growing understanding of an intriguing link between the gut microbiome and ICI outcomes. Multiple studies have demonstrated a connection between microbial metagenomic and metatranscriptomic patterns and ICI efficacy in malignant melanoma, lung and colorectal cancer. The immunomodulatory effect of the gut microbiome can have a real effect on the biological background of irAEs as well. Furthermore, specific microbial signatures and metabolites might be associated with the onset and severity of toxicity symptoms. By identifying these biological factors, novel biomarkers can be used in clinical practice to predict and manage potential irAEs. This comprehensive review aims to summarize the clinical aspects and biological background of ICI-related irAEs and their potential association with the gut microbiome and metabolome. We aim to explore the current state of knowledge on the most important and reliable irAE-related biomarkers of microbial origin and discuss the intriguing connection between ICI efficacy and toxicity.
免疫检查点抑制剂（ICIs）改变了我们对肿瘤管理的看法。抗程序性死亡配体-1（PD-L1）免疫疗法的组合已成为许多晚期癌症的标准治疗方法，包括一线治疗。除了改善抗肿瘤免疫外，免疫检查点抑制剂（ICIs）的作用机制还暴露了一种新的毒性特征，称为免疫相关不良事件（irAEs）。这种新的毒性可以损害任何器官，但皮肤、消化和内分泌系统是最常受累的器官。大多数 ICI 相关毒性症状较轻，但有些症状严重，需要多学科的副作用管理。了解各种形式的免疫相关毒性以及迅速改变治疗技术以降低发生严重 irAEs 的概率已成为肿瘤学护理的重点。近年来，人们越来越了解肠道微生物组与 ICI 结果之间的有趣联系。多项研究表明，微生物宏基因组和宏转录组模式与恶性黑色素瘤、肺癌和结直肠癌中的 ICI 疗效之间存在联系。肠道微生物组的免疫调节作用可能对 irAEs 的生物学背景产生真正的影响。此外，特定的微生物特征和代谢物可能与毒性症状的发生和严重程度有关。通过识别这些生物学因素，可以在临床实践中使用新型生物标志物来预测和管理潜在的 irAEs。本综述旨在总结 ICI 相关 irAEs 的临床方面和生物学背景及其与肠道微生物组和代谢组的潜在关联。我们旨在探讨微生物起源的最重要和可靠的 irAE 相关生物标志物的最新知识状态，并讨论 ICI 疗效和毒性之间的有趣联系。
