免疫检查点阻断治疗反应的基因组相关性。
Genomic correlates of response to immune checkpoint blockade.
机构信息
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
出版信息
Nat Med. 2019 Mar;25(3):389-402. doi: 10.1038/s41591-019-0382-x. Epub 2019 Mar 6.
Despite impressive durable responses, immune checkpoint inhibitors do not provide a long-term benefit to the majority of patients with cancer. Understanding genomic correlates of response and resistance to checkpoint blockade may enhance benefits for patients with cancer by elucidating biomarkers for patient stratification and resistance mechanisms for therapeutic targeting. Here we review emerging genomic markers of checkpoint blockade response, including those related to neoantigens, antigen presentation, DNA repair, and oncogenic pathways. Compelling evidence also points to a role for T cell functionality, checkpoint regulators, chromatin modifiers, and copy-number alterations in mediating selective response to immune checkpoint blockade. Ultimately, efforts to contextualize genomic correlates of response into the larger understanding of tumor immune biology will build a foundation for the development of novel biomarkers and therapies to overcome resistance to checkpoint blockade.
尽管免疫检查点抑制剂有令人印象深刻的持久反应，但它们并不能为大多数癌症患者提供长期获益。了解反应和对检查点阻断的耐药性的基因组相关性，通过阐明患者分层的生物标志物和治疗靶点的耐药机制，可能会增加癌症患者的获益。在这里，我们综述了检查点阻断反应的新兴基因组标志物，包括与新抗原、抗原呈递、DNA 修复和致癌途径相关的标志物。有强有力的证据表明，T 细胞功能、检查点调节剂、染色质修饰因子和拷贝数改变在介导对免疫检查点阻断的选择性反应中也发挥作用。最终，将反应的基因组相关性纳入肿瘤免疫生物学的更广泛理解中的努力，将为开发克服检查点阻断耐药性的新型生物标志物和疗法奠定基础。
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