免疫检查点
医学
转录组
外显子组
基因组学
封锁
CTLA-4号机组
外显子组测序
微卫星不稳定性
生物信息学
计算生物学
免疫疗法
免疫系统
基因组
免疫学
生物
T细胞
基因
遗传学
突变
内科学
基因表达
等位基因
受体
微卫星
作者
Krijn K. Dijkstra,Paula Voabil,Ton N. Schumacher,Emile E. Voest
出处
期刊:JAMA Oncology
[American Medical Association]
日期:2016-11-01
卷期号:2 (11): 1490-1490
被引量:68
标识
DOI:10.1001/jamaoncol.2016.2214
摘要
Checkpoint blockade therapy targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death protein 1 pathways (PD-1/PD-L1) have achieved success in treating a number of malignancies. However, only a subset of patients responds to these therapies, and optimization of patient selection for treatment is imperative to avoid adverse effects without clinical benefit and keep costs manageable.The past few years have witnessed checkpoint inhibition becoming a first-line treatment option with US Food and Drug Administration approvals for various tumor types. Genomic analyses (whole genome, exome, and transcriptome) have been instrumental in identifying a genetic profile associated with sensitivity to checkpoint inhibitors. Therapy outcome is determined at various levels: (1) the degree of tumor "foreignness," as reflected by mutational burden and expression of viral genes, (2) the composition and activity of a preexisting immune infiltrate, and (3) mechanisms of tumor escape from immune surveillance. In addition, there are opportunities for genomic analyses of genetic polymorphisms and the gut microbiome that may be associated with clinical response to therapy.Genomics provides powerful tools for the identification of biomarkers for response to immune checkpoint blockade, given their potential to analyze multiple parameters simultaneously in an unbiased manner. This offers the opportunity for genomics- and transcriptomics-based selection of patients for rationally designed therapy with immune checkpoint inhibitors.
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