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免疫疗法的疗效和毒性:回顾患者可实施策略背后的证据。

Immunotherapy efficacy and toxicity: Reviewing the evidence behind patient implementable strategies.

机构信息

Department of Medical Oncology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium.

Department of Medical Oncology, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium; Department of Internal Medicine, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium.

出版信息

Eur J Cancer. 2024 Sep;209:114235. doi: 10.1016/j.ejca.2024.114235. Epub 2024 Jul 22.

Abstract

The use of immune checkpoint inhibitors (ICI) in cancer treatment is expanding, offering promising outcomes but with an important risk of immune-related adverse events (irAEs). These events, stemming from an overstimulated immune system attacking healthy cells, can necessitate immunosuppressant treatment, disrupt treatment courses, and impact patients' quality of life. The analysis of ICI efficacy data has led to a better understanding of the characteristics of responders. Similarly, we are gaining clearer insights into the characteristics of patients who develop irAEs, prompting an increasing emphasis on modifiable factors associated with irAE risk. These factors include lifestyle choices and the composition of the gut microbiome. Despite comprehensive reviews exploring the microbiome's role in therapy efficacy, understanding its connection with immune-related toxicity remains incomplete. While endeavours to identify predictive biomarkers continue, lifestyle modifications emerge as a promising avenue for enhancing treatment outcomes. This review consolidates the current evidence regarding the impact of the gut microbiome on irAE occurrence. Furthermore, it focuses on actionable strategies for mitigating these adverse events, elucidating the evidence supporting dietary adjustments, supplementation, medication management, and physical activity. With the expanding range of indications for ICI therapy, a significant proportion of oncology patients, including those in early disease stages, are now exposed to these treatments. Acknowledging the importance of averting irAEs in this context, our review offers timely insights crucial for addressing the evolving challenges associated with immunotherapy across diverse oncological settings.

摘要

免疫检查点抑制剂 (ICI) 在癌症治疗中的应用正在不断扩大,为患者带来了有希望的治疗效果,但也存在重要的免疫相关不良反应 (irAE) 风险。这些不良反应源于过度激活的免疫系统攻击健康细胞,可能需要免疫抑制剂治疗,中断治疗进程,并影响患者的生活质量。对 ICI 疗效数据的分析使我们更好地了解了应答者的特征。同样,我们也越来越清楚地认识到发生 irAE 的患者的特征,这促使人们越来越关注与 irAE 风险相关的可改变因素。这些因素包括生活方式选择和肠道微生物组的组成。尽管有全面的综述探讨了微生物组在治疗效果中的作用,但对其与免疫相关毒性之间联系的理解仍不完整。虽然仍在努力寻找预测性生物标志物,但生活方式的改变似乎是提高治疗效果的有前途的途径。

本综述总结了目前关于肠道微生物组对 irAE 发生影响的证据。此外,它还重点介绍了减轻这些不良反应的可行策略,阐明了支持饮食调整、补充剂、药物管理和体育活动的证据。随着 ICI 治疗适应证的不断扩大,包括早期疾病阶段在内的相当一部分肿瘤患者现在都接受这些治疗。鉴于在这种情况下避免 irAE 的重要性,我们的综述为应对免疫治疗在不同肿瘤学环境中不断出现的挑战提供了及时的见解。

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