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通过基因组学预测免疫疗法反应。

Predicting immunotherapy response through genomics.

机构信息

Department of Medical Imaging, Hematology, and Oncology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, 14040-900, Brazil.

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.

出版信息

Curr Opin Genet Dev. 2021 Feb;66:1-9. doi: 10.1016/j.gde.2020.11.004. Epub 2020 Dec 8.

Abstract

Immune checkpoint inhibitors (ICI) aim to restore the immune system anti-tumor function by blocking two inhibitory axes: CTLA-4/CD28 and PD1/PDL1. ICI is established as a treatment option for multiple cancers, but their remarkable clinical impact is observed only in a fraction of patients. Together with their adverse effects and high cost, it's imperative to identify patients who are likely to benefit from this type of treatment. Genomic features represent promising candidates as predictive biomarkers of response to ICI, with agnostic FDA-approvals of an anti-PD1 drug for tumors with microsatellite instability and tumors with a high mutational burden. Other genomic markers are also emerging to help refine patient selection. In this review, we discuss recent progress in genomic biomarkers development and its challenges, with a focus on alterations in the neoantigen burden, immune, and oncogenic pathways.

摘要

免疫检查点抑制剂(ICI)通过阻断 CTLA-4/CD28 和 PD1/PDL1 两个抑制轴,旨在恢复免疫系统的抗肿瘤功能。ICI 已被确立为多种癌症的治疗选择,但它们的显著临床效果仅在一部分患者中观察到。此外,它们还存在不良反应和高成本,因此必须确定哪些患者可能从这种治疗中受益。基因组特征是作为 ICI 反应预测生物标志物的有前途的候选者,FDA 批准了一种抗 PD1 药物用于微卫星不稳定的肿瘤和高突变负担的肿瘤,这是一个不依赖于认知的决定。其他基因组标志物也在不断涌现,以帮助完善患者选择。在这篇综述中,我们讨论了基因组生物标志物开发的最新进展及其挑战,重点是新抗原负担、免疫和致癌途径的改变。

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