Molecular Immunology Laboratory, Institut Jules Bordet, Université Libre de Bruxelles, Brussels (Anderlecht), Belgium.
Curr Opin Oncol. 2022 Sep 1;34(5):579-586. doi: 10.1097/CCO.0000000000000891.
Here, we reviewed the recent breakthroughs in the understanding of predictive biomarkers for immune checkpoint inhibitors (ICI) treatment.
ICI have revolutionized cancer therapy enabling novel therapeutic indications in multiple tumor types and increasing the probability of survival in patients with metastatic disease. However, in every considered tumor types only a minority of patients exhibits clear and lasting benefice from ICI treatment, and due to their unique mechanism of action treatment with ICI is also associated with acute clinical toxicities called immune related adverse events (irAEs) that can be life threatening. The approval of the first ICI drug has prompted many exploratory strategies for a variety of biomarkers and have shown that several factors might affect the response to ICI treatment, including tumors intrinsic factors, tumor microenvironment and tumor extrinsic or systemic factor. Currently, only three biomarkers programmed death-ligand 1 (PD-L1), tumor microenvironment and microsatellite instability had the US Food and Drug Administration-approbation with some limitations.
The establishment of valid predictive biomarkers of ICI sensitivity has become a priority to guide patient treatment to maximize the chance of benefit and prevent unnecessary toxicity.
在这里，我们回顾了近年来对免疫检查点抑制剂 (ICI) 治疗预测生物标志物的理解的突破。
ICI 已经彻底改变了癌症治疗，为多种肿瘤类型带来了新的治疗适应症，并增加了转移性疾病患者的生存机会。然而，在每一种被考虑的肿瘤类型中，只有少数患者从 ICI 治疗中明显和持久地受益，并且由于其独特的作用机制，ICI 的治疗也与被称为免疫相关不良事件 (irAEs) 的急性临床毒性相关，这些毒性可能危及生命。第一个 ICI 药物的批准促使人们对各种生物标志物进行了许多探索性策略的研究，并表明有几个因素可能会影响对 ICI 治疗的反应，包括肿瘤内在因素、肿瘤微环境和肿瘤外在或全身因素。目前，只有三个生物标志物程序性死亡配体 1 (PD-L1)、肿瘤微环境和微卫星不稳定性获得了美国食品和药物管理局的批准，但存在一些局限性。
建立有效的 ICI 敏感性预测生物标志物已成为优先事项，以指导患者治疗，最大限度地提高获益机会并防止不必要的毒性。
