Centre for Precision Health, Edith Cowan University, Joondalup, WA, Australia.
School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia.
Front Immunol. 2023 Jan 11;13:991433. doi: 10.3389/fimmu.2022.991433. eCollection 2022.
The use of immune checkpoint inhibitors (ICIs) has evolved rapidly with unprecedented treatment benefits being obtained for cancer patients, including improved patient survival. However, over half of the patients experience immune related adverse events (irAEs) or toxicities, which can be fatal, affect the quality of life of patients and potentially cause treatment interruption or cessation. Complications from these toxicities can also cause long term irreversible organ damage and other chronic health conditions. Toxicities can occur in various organ systems, with common observations in the skin, rheumatologic, gastrointestinal, hepatic, endocrine system and the lungs. These are not only challenging to manage but also difficult to detect during the early stages of treatment. Currently, no biomarker exists to predict which patients are likely to develop toxicities from ICI therapy and efforts to identify robust biomarkers are ongoing. B cells and antibodies against autologous antigens (autoantibodies) have shown promise and are emerging as markers to predict the development of irAEs in cancer patients. In this review, we discuss the interplay between ICIs and toxicities in cancer patients, insights into the underlying mechanisms of irAEs, and the involvement of the humoral immune response, particularly by B cells and autoantibodies in irAE development. We also provide an appraisal of the progress, key empirical results and advances in B cell and autoantibody research as biomarkers for predicting irAEs. We conclude the review by outlining the challenges and steps required for their potential clinical application in the future.
免疫检查点抑制剂（ICIs）的应用发展迅速，为癌症患者带来了前所未有的治疗益处，包括提高患者生存率。然而，超过一半的患者经历免疫相关不良事件（irAEs）或毒性反应，这些反应可能是致命的，影响患者的生活质量，并可能导致治疗中断或停止。这些毒性反应的并发症也会导致长期不可逆的器官损伤和其他慢性健康问题。毒性反应可发生在各种器官系统中，常见于皮肤、风湿、胃肠道、肝脏、内分泌系统和肺部。这些不仅难以管理，而且在治疗早期也难以发现。目前，没有生物标志物可预测患者是否会因 ICI 治疗而产生毒性反应，因此正在努力寻找稳健的生物标志物。B 细胞和针对自身抗原的抗体（自身抗体）显示出了希望，并成为预测癌症患者 irAEs 发展的标志物。在这篇综述中，我们讨论了 ICI 和癌症患者毒性反应之间的相互作用、irAEs 潜在机制的见解，以及体液免疫反应的参与，特别是 B 细胞和自身抗体在 irAE 发展中的作用。我们还评估了 B 细胞和自身抗体作为预测 irAEs 的生物标志物的研究进展、关键实证结果和进展。最后，我们概述了其未来潜在临床应用所需的挑战和步骤。
